PH12014501744B1 - Pesticidal compositions and processes related thereto - Google Patents

Pesticidal compositions and processes related thereto Download PDF

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PH12014501744B1
PH12014501744B1 PH12014501744A PH12014501744A PH12014501744B1 PH 12014501744 B1 PH12014501744 B1 PH 12014501744B1 PH 12014501744 A PH12014501744 A PH 12014501744A PH 12014501744 A PH12014501744 A PH 12014501744A PH 12014501744 B1 PH12014501744 B1 PH 12014501744B1
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Philippines
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alkyl
spp
phenyl
cdcl
haloalkyl
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PH12014501744A
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PH12014501744A1 (en
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Erich W Baum
Gary D Crouse
Dent William Hunter
Thomas C Sparks
Lawrence C Creemer
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Dow Agrosciences Llc
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/86—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage

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Abstract

This document discloses molecules having the following formulas ("Formula One" and "Formula Two" and "Formula Three") The Ar1, Het, Ar2, R1, R2, R3, R4, and R5 are further described herein.

Description

- : PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO | ps >
FIELD OF THE INVENTION
The invention disclosed in this document is related to the field of processes to produce molecules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules, and processes of using such molecules to control pests.
BACKGROUND OF THE INVENTION
Pests cause millions of human deaths around the world each year. Furthermore, there
I5 are more than ten thousand species of pests that cause losses in agriculture. The world-wide agricultural losses amount to billions of U.S. dollars each year. : : Termites cause damage to all kinds of private and public structures. The world-wide : termite damage losses amount to billions of U.S. dollars each year.
Stored food pests eat and adulterate stored food. The world-wide stored food losses © 20 amount to billions of U.S. dollars each year, but more importantly, deprive people of needed food.
There is an acute need for new pesticides. Certain pests are developing resistance to pesticides in current use. Hundreds of pest species are resistant Lo one or more pesticides. The : development of resistance to some of the older pesticides, such as DDT, the carbamates, and the organophosphates, is well known, but resistance has even developed to some of the newer pesticides.
Therefore, for many reasons, including the above reasons, a need exists for new pesticides.
DEFINITIONS
The examples given in the definitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a substituent should comply with chemical honding rules and steric compatibility constraints in relation to the particular molecule to which it is attached.
“Acaricide Group™ is defined under the heading “ACARICIDES”. “Al Group™ is defined after the place in this document where the “Ilerbicide Group™ is defined. “Alkenyl” means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, peatenyl, and hexenyl. “Alkenyloxy” means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy. “Alkoxy” means an alky! further consisting of a carhon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, buloxy, isobutoxy, and tert-butoxy. “Alkyl” means an acyclic, saturated, branched or unbranched, substituent consisting ; of carbon and hydrogen, for example, methyl, ethyl, propyl, isopropyl, butyl, and tert-butyl. “Alkynyl” means an acyclic, unsaturated (at least one carbon-carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl. “Alkynyloxy” means an alkynyl further consisting of a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy. heptynyloxy. and octynyloxy. “Aryl” means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl. “Cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at least onc carbon- carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norhornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl. “Cycloalkenyloxy” means a cycloalkenyl further consisting of a carbon-oxygen single bond, [or example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and : bicyclo[2.2.2]octenyloxy. “Cycloalkyl” means a monocyclic or polycyclic, saturated substituent consisting of : carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl. “Cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and bicyclo[2.2.2Joctyloxy. “Fungicide Group™ is defined under the heading “FUNGICIDES.” “Halo” means (luoro, chloro, bromo, and iodo. :
“Haloalkoxy™ means an alkoxy further consisting of, from one to the maximum possible number ol identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2- tetralluoroethoxy, and pentafluoroethoxy. “Haloalkyl’”™ means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2- difluoropropyl, chloromethyl, trichloromethyl, and [,1,2,2-tetrafluorocthyl. ; “Herbicide Group” is defined under the heading “HERBICIDES.” “Heterocyclyl” means a cyclic substituent that may be fully saturated, partially : unsaturated, or fully unsaturated, where the cyclic structure contains al least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen. Ixamples of aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazoly! cinnolinyl, furany!, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls include, but are not : limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, and tetrahydropyranyl. Examples of partially unsaturated heterocycelyls include, but are not limited to, 1,2,34-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro- LH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[1,3,4}-oxadiazolyl. “Insecticide Group” is defined under the heading “INSECTICIDES.” “Nematicide Group” is delined under the heading “NEMATICIDES™ “Synergist Group™ is defined under the heading “SYNERGISTIC MIXTURES
AND SYNERGISTS”
DETAILED DESCRIPTION OF THE INVENTION
This document discloses molecules having the following formulas (“Formula One” &“Formula Two” and “Formula Three”): (In the following formulas the nitrogens are numbered |, 2, and 3, solely for the purpose of identifying them and being able to refer to them throughout this document for clarity purposes)
Rl R2 aS Ay N2 _ 23
N3,
Formuia | Re
Ri RI R5
Ar] Mae N Aas i a Sar Nos
N3~ RS ! ? 3
Rs “R4
Formula 2 Formula 3 wherein: (a) Ary is
HH furanyl, phenyl, pyridaziny!, pyridyl, pyrimidinyl, thienyl, or 2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl, have one or more substituents independently selected from H, F, Cl, Br, I, CN, NO», C,-C¢ alkyl, C,-Cq haloalkyl, C;-Cg cycloalkyl, C3-Cg halocycloalkyl, C;-Cy cycloalkoxy, C3-Ce halocycloalkoxy, C;-Cs alkoxy, C;-Cg haloalkoxy, Cy-Cy alkenyl, C,-Cg alkynyl, S(=0),(C-
Cs alkyl), S(=0)a(C-Cs haloalkyl), 0SO(C;-Cg alkyl), OSO(C-Cs haloalkyl),
C(=O)NRRy, (Ci-Cs alkyINRRy, C(=0)(C;-Cs alkyl), C(=0)0(C;-Ce alkyl), C(=0)C-Cs haloalkyl), C(=0)0(C-Cg haloalkyl), C(=0)(C3-Cq cycloalkyl), C(=0)0(C;3-C cycloalkyl),
C(=0)(C2-Co alkenyl), C(=0)O(C,-Cy alkenyl), (C;-Cq alkyl)O(C,-Cg alkyl), (C,-Cs alkyDS(C,-Cg alkyl), C(=0)C;-Cg alkyDC(=0)O(C,-Cs alkyl), phenyl, phenoxy, substituted phenyl, and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, CL, Br, I, CN, NO, Ci-Cs alkyl, C-Cq haloalkyl, C3-Cg cycloalkyl, C3-Cg halocycloalkyl, C3-Cs cycloalkoxy, C3-Cg halocycloalkoxy, C-Cq alkoxy, C;-Cq haloalkoxy, Ca-C alkenyl, C3-Cq alkynyl, S(=0)o(C)-
Co alkyl), S(=0)a(C1-Cs haloalkyl), 0S0y(C-Ce alkyl), 0SOL(C,-Cs haloalkyl),
C(=0)NRRy, (Cy-Cg alkyl)NRR,, C(=0)(C;-Cg alkyl), C(=0)O(C-Cg alkyl), C(=0XC-Cs haloalkyl), C(=0)O(C-C haloalkyl), C(=0)(C;-Cs cycloalkyl), C(=0)0(C;3-Cg cycloalkyl),
C(=0XC2-Cs alkenyl), C(=0)O(C,-Cy alkenyl). (C1-Co alkyhO(C,-C alkyl). (C1-Ce alkyDS(Cy-Cp alkyl), C=O) CC alkyDC(=0)O(C-C alkyl) phenyl, and phenoxy; (b) Het is a 5 or 6 membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur, or oxygen, and where Ar; and Ar; are not ortho to cach other (but may be meta or para, such as, for a five membered ring they are 1.3 and for a 6 membered ring they are either 1,3 or 1,4), and where said heterocyclic ring may also be substituted with one or more substituents independently selected from H, F, C1, Br, I, CN, NO,, oxo, (|-Cq alkyl, C,-Cg haloalkyl, C;-
Cy cycloalkyl, C3-Cg halocycloalkyl, C;-Cg cycloalkoxy, C3-C halocycloalkoxy, C-Cq alkoxy, C;-Cg haloalkoxy, Ca-Cs alkenyl, C,-Cg alkynyl, S(=0),(C}-Cg alkyl), S(=0).(C,-Ce haloalkyl), OSO2(C,-Cg alkyl), OSO(C-Cg haloalkyl), C(=0)NRR,, (C)-Cq alkyl)NR(R,,
C(=0XC-Cy alkyl), C(=0)O(C Cy alkyl), C(=0)C,-Cq haloalkyl), C(=0)Y(C-Cq haloalkyl), C(=0)C;-Cq cycloalkyl), C(=0)O0(C;-Cg cycloalkyl), C(=0)C2-C, alkenyl),
C(=0)0(C,-Ce alkenyl), (C4-Cg alkyDO(C-Cg alkyl), (C1-Cg alkyDS(Cy-Cg alkyl), C=0)(Cy-
IS Cg alky)C(=0)O(C;-Cg alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from I, F, Cl, Br, [, CN, NO,, C;-Cs alkyl, Cy-Cq haloalkyl, C;-Cs cycloalkyl, C3-Cg halocycloalkyl, C3-Cg cycloalkoxy, C;-Ce halocycloalkoxy, Cy-Cs alkoxy, Ci-Cg haloatkoxy., Ca-Co alkenyl, C2-Cs alkynyl, S(=0),(C-
Cg alkyl), S(=0),4(C;-Cs haloalkyl), OSO:(C,-Cy alkyl), OSO2(C,-Cg haloalkyl), C(=O)H,
C(=0)NRRy, (Cy-Cq alkyhNRR,, C(=0)C;-C alkyl), C(=0)0(C-Cg alkyl), C(=0)C-Cs haloalkyD), C(=0)O(C,-C haloalkyl), C(=0)(C;-Cs cycloalkyl), C(=0)O(C;-Cy cycloalkyl),
C(=0)(Ca-Cs alkenyl), C(=0)(Co-Cg alkenyl), (C1-Cy alkyDO(Cy-Cg alkyl), (C1-Co alkyDS(C-Ce alkyl), C(=0)(C1-Ce alkyl)C(=0)O(C,-Cs alkyl), phenyl, and phenoxy; © Anis (Nn furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or : (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl, have one or \ more substituents independently selected from IH, I, Cl, Br, I, CN, NO, C,-Cq alkyl, C;-C,q \ haloalkyl, C3-Cg cycloalkyl, C3-Cg halocyeloalkyl, C3-Cs cycloalkoxy, C;-Cg i halocycloalkoxy, Cy-Cq alkoxy, C-Ce haloalkoxy, C;-Cg alkenyl, C,-Cy, alkynyl, S(=0)n(C-
Cs alkyl), S(=0)a(C-Cg haloalkyl), OSO(C-Cg alkyl), OSQ2(C;-Cq haloalkyl),
C(=0)NRRy, (C-Co alkyDNRR,, C(=0)(C}-Cq alkyl), C(=0)O(C,-Cq alkyl), C(=0)(C-Co haloalkyl), C(=0)O(C-Ce haloalkyl), C(=0)(C3-Cs cycloalkyl), C(=0)O(C;-Ce cycloalkyl), :
C(=0)C7-Cq alkenyl), C(=0)O(C,-Cq alkenyl), (C-Cq alkyO(Cy-Cg alkyl), (C1-Cs alkyhS(C,-Ce alkyl), C(=0)(C-Ce alkyDC(=0)O(C,-Cy alkyl), phenyl, phenoxy, substituted ; phenyl and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, C1, Br, [, CN, NO,, C,-Cg alkyl, C;-Cq haloalkyl, C3-Cs cycloalkyl, C3-Ce halocycloalkyt, C3-Cq cycloalkoxy, Cy-Ce halocycloalkoxy, C4-Cg alkoxy, Cy-Cg haloalkoxy, Cy-Cg alkenyl, C,-Cg alkynyl, S(=0),(C-
Ce alkyl), S(=0)a(C-Co haloalkyl), OSO,(C-Cy alkyl), OSO,(C,-Cy haloalkyl), C=O),
C(=O)NRRy, (C-Cq alkyDNR Ry, C(=0)C-Cq alkyl), C(=0)O(C,-Cq alkyl), C(=0)C,-Cs haloalkyl), C(=0)O(C4-C, haloalkyl), C(=0)(C3-Cy, cycloalkyl), C(=0)O(C3-Cy cycloalkyl),
C(=0)(C-Cg haloalkyl), C(=0)(C;-Ce alkenyl), C(=0)0(C1-Cs alkenyl), (C;-Cg alkyDO(C-
Cealkyh), (C-Co alkyD)S(Cy-Cs alkyl), C(=0)C)-Cy alkyDC(=0)O(C;-Cs alkyl), phenyl, and phenoxy; (d) Rl is selected from H, CN, F, Cl, Br, I, C;-Cg alkyl, C;-Cg cycloalkyl, C3-Cg cycloalkoxy, Ci-Cq alkoxy, C2-Cyg alkenyl, C2-Cg alkynyl, S(=0),(Cy-Cs alkyl), OSOx(C;1-Cs alkyl), C=O)NRRy, (C-Cs alky)NR(Ry, C(=0)(C,-Cs alkyl), C(=0)O(Cy-Cg alkyl).
C(=0)C;3-Cs cycloalkyl), C(=0)0(C3-Cg cycloalkyl), C(=0)(C2-Cs alkenyl), C(=0)O(C,-Cs alkenyl), (C-Cs alky)O(C,-Cg alkyl), (C-Ce alky)S(C,-Cy alkyl), C(=0)(C,-Ce alkyDC(=0)O(C1-Cg alkyl), phenyl, or phenoxy, : wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, : and phenoxy, are optionally substituted with one or more substituents independently selected from F, CI, Br, I, CN, NO, oxo, C-C alkyl, C;-Cg haloalkyl, C3-Cg cycloalkyl, C3-Cg : halocycloalkyl, C3-Cq cycloalkoxy, C3-Ce halocycloalkoxy, C,-Cs alkoxy, C;-Cg haloalkoxy,
CC alkenyl, C5-Cg alkynyl, S(=0)a(C)-Ce alkyl), S(=0)a(C;-Cs haloalkyl), 0SO,(C,-Cs alkyl), OSO2(C,-Cy haloalkyl), C(=0)NRRy, (C1-Cg alkyDNRRy, C(=0)(C(-Cg alkyl), ]
CEOYO(C-Co alkyl), C(=0)(C,-Cy haloalkyl), C(=0)O(C Cg haloalkyl), C(=0)(C;-Cs cycloalkyl), C(=0)X(C3-Cs cycloalkyl), C(=0)(C,-Cs alkenyl), C(=0)O(Ca-Ce alkenyl), (C)-
Co alkyD)O(C1-Cy alkyl), (C-Co alkyDS(C)-Cy alkyl), C(=0)C1-Cq alky)C(=0)O(C,-Co alkyl), phenyl, and phenoxy;
(e) R2 is 11, C-Cy alkyl, C3-Cq cycloalkyl, C,-Cg alkenyl, C,-Cg alkynyl, C(=0)H,
C(=0)C)-Cg alkyD), C(=0)O(C-Cs alkyl), C(=0)C3-Cq cycloalkyl), C(=0HO(C5-Cq cycloalkyl), C(=0X CC alkeny!), C(=0)0(C2-Cq alkenyl), (C-Cs alkyDO(C-Ce alkyl), (C1-Co alkyDS(C-Cq alkyl), C(=0)C-Cq alkyDC(=0)O(Cy-Cg alkyl), phenyl, C1-Cq alkylphenyl, C-Ce alkyl-O-phenyl, C(=O)ITet-1, et-1, C-Ce alkyllet-1, or C;-Ce alkyl-O-
Het-1, wherein cach alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and let-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1,
CN, NOs, NR(R,, C-Ce alkyl, C-Cs haloalkyl, C;-Cq cycloalkyl, C;-Cq halocycloalkyl, Cs-
Cg cycloalkoxy, Ci-Cg halocycloalkoxy, C-Cg alkoxy, Ci-Cg haloalkoxy, Co-Cg alkenyl, Cs-
Cs cycloalkenyl, C2-Cq alkynyl, S(=0)a(C-Cs alkyl), S(=0)a(C-Cs haloalkyl), OSO(C,-Cs alkyl), OSO02(C,-Cs haloalkyl), C(=0)H, C(=0)NRRy, (C-Cs alkyl)NR(Ry, C(=0)(Cy-Cs alkyl), C(=0)O(C;-Cg alkyl), C(=0)C-Cg haloalkyl), C(=0)O(C,-C haloalkyl), C(=0)C;-
Ce cycloalkyl), C(=0)0(C3-Ce cycloalkyl), C(=0)Ca-Cs alkenyl), C(=O)O(C>-Cy alkenyl), (Cy-Cq alkyDO(C-Cy alkyl), (C1-Co alkyDS(C4-Cy alkyl), C(=0)C-Cy alkyDC(=0)X(C-Co alkyl), phenyl, phenoxy, and Het-1; (f) R3 is (0}-Cg alkyl, C3-Cg cycloalkyl, C,-Cg alkenyl, C-Cy alkynyl, C(=0)1,
C(=0)(C-Co alkyl). C(=0)O(C-Cs alkyl), C(=0)(C3-Cs cycloalkyl), C(=0)O(C3-Ce cycloalkyl), C(=0)(C,-Cs alkenyl), C(=0)0(C-Cy alkenyl), (C1-Cs alkyDO(C,-Cg alkyl), (Cr-Ce alkyDS(Cy-Cy alkyl), C(=0)(C,-Cy alkyDC(=0)O(Cy-Cg alkyl), phenyl, Ci-Cq alkylphenyl, C;-Ce alkyl-O-phenyl, C(=0)et-1, Het-1, C,-Cq alkylHet-1, C-Cg alkyl-O-
C(E=0)Ch-C alkyl-O-Cy-Cq alkyl, C-Coalkyl-O-C(=0)C,-Cs alkyl-O-C)-Cg alkyl-O- C;-Cg alkyl, C-Ce alkyl-O-C(=0)C;-Cs alkyl-O-C,-Cs haloalkyl, C;-Cg alkyl-O-C(=0)C,-Cs alkyl-
NRIC(EO0)-0O-phenyl, Ci-Ce alkyl-O-C(=0)C,-Cg alkyl-N(R,)C(=0)-0-C;-Cq alkylpheny], :
C1-Co alkylC(=0)IN(R,)C -Cg alkyl, C-Ce alkyl C(=0)N(R)C,-Cg alkylTlet- 1 C(=0)-0-C-Ce alkyl, C-Co alkylC(=0)N(R,)C-Cg alkylHet-1, Ci-CgalkylC(=0)Het-1, C,-Cg alkylC(=0)N(R)C;-Co alky (N(R (RC (=0)OH), C}-Co alkyl C(=0)N(R,)C-Ce : alkyIN(R(R,), C-Cq alkylC(=0)N(R,)C;-Cg alkyIN(R)C(=0)-0-C-Cg alkyl, C-C alkylC(=0)N(R)C-Cy alkyl(N(R)C(=0)-0-C-Cy alky)(C(=0)OIT), Ci-Cg alkyl C(=0)H Het 1C(=0)-0-C4-Cs alkyl, Cy-Cg alkyl-0-C(=0)-0-C-C alkyl, C-Cg alkyl-0-C(=0)C;-Cs alkyl, C;-Co alkyl-O-C(=0)C;-Cq cycloalkyl, C1-Cgalkyl-O-C(=0)Het- 1, C1-Cq alkyl-O-
C(=0)C,-Co alky-N(R)C(=0)-0-C,-Ce alkyl, C;-Cg alkyl-NRR,, or C;-Cg alkyl-O-Het-1, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Llet-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1,
CN, NO2, NRRy, C-Cq alkyl, C;-Cq haloalkyl, C3-Cq cycloalkyl, Cs-Cg halocycloalkyl, Cs-
Cs cycloalkoxy, C3-Ce halocyeloalkoxy, C-Cg alkoxy, C-Cg haloalkoxy, C,-C alkenyt, C;-
Cy cycloalkenyl, Co-Cg alkynyl, S(=0)a(C;-Cy alkyl), $(=0),(C-Cs haloalkyl), OSO(C-Cs alkyl), OSO(C,-Cé haloalkyl), C(=O)H, C(=0)OI1, C(=0)NRyRy, (C,-Cs alkyl)NR(R,,
C(=0)C,-Cg alkyl), C(=0)O(C,-Cq alkyl), C(=0)(C,-Cs haloalkyl), C(=0)O(C,-Cq haloalkyl), C(=0)(C3-Cg cycloalkyl), C(=0)0(C;-Cq cycloalkyl), C(=0)(Cy-C,, alkenyl),
C=0)O(C-Cq alkenyl), (C;-Cy alkyhO(C,-Cg alkyl), (C-Cg alkyDS(Cy-Cq alkyl), C(=0)(C-
Ce alkyDC(=0)O(C Cg alkyl), phenyl, phenoxy, Si(C-Ce alkyl); S(=0).NRRy, and Iet-1; (2) R4 is H, C-Cg alkyl, C3-Cg cycloalkyl, C2-Cy alkenyl, Cy-Cq alkynyl, C=O),
C(=0XC,-Cg alkyl), C(=O0)YO(C-Cs alkyl), C(=0)(C;-Cq cycloalkyl), C(=0)O(C3-Co cycloalkyl), C(=0)C2-C alkenyl), C(=0)O(C,-Cy alkenyl), (C-Ce alkyl )O(C,-Cg alkyl), (C-Ce alkyDS(C4-Ce alkyl), C(=0)(C-Cs alkyHC(=0)O(Cy-Cs alkyl), phenyl, C-Cs alkylphenyl, C(-Cg alkyl-O-phenyl, C(=O)llet-1, Het-1, C;-C¢ alkylHet-1, or C;-Cy alkyl-O-
Het-1, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-1 are optionally substituted with onc or more substituents independently selected from F, CI, Br, 1, ]
CN, NO3, NRRy, C}-Cg alkyl, Cy-Cg haloalkyl, C3-Cq cycloalkyl, Ci-Cg halocycloalkyl, Cs-
Cg cycloalkoxy, C'3-Ce halocycloatkoxy, C,-Cg alkoxy, C;-Cg haloalkoxy, C2-Cs alkenyl, C;-
Cs cycloalkenyl, C2-Cg alkynyl, $(=0)4(C;-Cg alkyl), S(=0)4(C-Cs haloalkyl), 0SO(Cy-Cq alkyl), OSOy(C)-Cg haloalkyl), C(=0)IT, C(=0)NRRy, (C-C¢ alkyhDNRRy, C(=0)(C;-Cs alkyl), C(=0)O(C,-Cs alkyl), C(=0)(C;-Cs haloalkyl), C(=0)O(C;-Cy haloalkyl), C(=0)Cs-
Cs cycloalkyl), C(=0)O(C;-Cg cycloalkyl), C(=0)(Cy-Cs alkenyl), C(=0)O(C,-Cs alkenyl), (C-Co alkyO(C-Cg alkyl), (Cy-Cg atkyDS(C)-C alkyl), C(=0)(C,-Cy alkyYC(=0Y(C,-Cy alkyl), phenyl, phenoxy, and Het-1; h) R5 is a | membered saturated or a 2 to 4 membered saturated or unsaturated hydrocarbyl linkage where said linkage may also be substituted with F, C1, Br, I, CN, NO, : oxo, NR(R,, C;-Cq alkyl, C-C haloalkyl, C3-Cq cycloalkyl, C3-Cq halocycloalkyl, C3-Cy cycloalkoxy, C3-Cg halocycloaltkoxy, C;-Cg alkoxy, C,-Cs haloalkoxy, (3-Ce alkenyl, C3-Cg cycloalkenyl, C2-Cq alkynyl, S(=0)a(C1-Cs alkyl), S(=0)a(C1-Cs haloalkyl), OSO(C,-Cs alkyl), OSO2(C,-Cs haloalkyl), C(=0)H, C(=0)OH, C(=0)NRR,, (C}-C¢ alky)NR\R,,
C(=0)(C'-Cs alkyl), C(=0)0(C1-Cy alkyl), C(=0)(C'-Cy haloalkyl), C(=0)0(Cy-C haloalkyl), C(=O)C;-Cq cycloalkyl), C(=0)0(C3-Cg cycloalkyl), C(=0)C;-Cs alkenyl),
C(=0)O(C-Cy alkenyl), (C,-Ce alkyDO(C1-Cq alkyl), (C-Cy alkyDS(Cy-Ce alkyl), C=O0)C)-
Ce alkyDC(=0O(C -Ce alkyl), phenyl, phenoxy, and Hlet-1, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, phenoxy, and [et-1, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO3, oxo, NRR,, C;-Cs alkyl, Cy-Cq haloalkyl, C3-Ce cycloalkyl, C3-C¢ halocycloalkyl, C3-C cycloalkoxy, C3-Cy halocycloalkoxy, C-Cg alkoxy,
C)-Cg haloalkoxy, Cy-Cg alkenyl, C;-C; cycloalkenyl, Cp-Cy alkynyl, $(=0),(C,-Cg alkyl),
S(=0)a(C-Cq haloalkyl), OSO,(C,-Ce alkyl), OSOC-Cg haloalkyl), C=O), C(=0)OL,
C(=0INRR,, (C}-Co alky)NR Ry, C(=0)(C-Cq alkyl), C(=0)X(C,-Cs alkyl), C(=0)(C-C haloalkyl), C(=0)O(C,-Ce haloalkyl), C(=0)C3-Cq cycloalkyl), C(=0YO(C;-Cs cycloalkyl),
C(=0)(C3-Cg alkenyl), C(=0)0O(Ca-Cq alkenyl), (C-Cq alkyDO(C-Cg alkyl), (C-Ce alkyDS(C-Cg alkyl), C(=0)(C-Cq alky)C(=0)O(C-Cy alkyl), phenyl, halophenyl, phenoxy, and Het-1;
I
(i) n=0,1,0r2; () Ry and Ry are independently selected from H, C;-Cq alkyl, C,-Cg haloalkyl,
C3-Cs cycloalkyl, C3-Cq halocycloalkyl, C,-Cq alkenyl, C2-Cg alkynyl, S(=0).(Ci-Ce alkyl),
S(=0)(C-Cg haloalkyl), OSC -Cs alkyl), OSO(C,-Cg haloalkyl), C(=0)H, C(=0XC;-Ce alkyl), C(=0)YO(C1-Cs alkyl), C(=0)(C;-Cq haloalkyl), C(=0)0(C1-Cg haloalkyl), C(=0XCs-
Ce cycloalkyl), C(=0)O(C;-C,, cycloalkyl), C(=0)C-Cs alkenyl), C(=0)O(C,-C alkenyl), (Ci-Cg alkyHO(C-Cg alkyl), (C1-Cg alkyNS(C-Cy alkyl), C(=0)C-Cq alkyDHC(=0)O(C-Ce alkyl), and phenyl, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, phenoxy, and 1let-1, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, NO, oxo, C-Cs alkyl, C;-Cg haloalkyl, C3-Cg cycloalkyl, C;-
Co halocycloalkyl, C3-Cq cycloalkoxy, C3-Cq halocycloalkoxy, C-Cg alkoxy, C;-Ce haloalkoxy, C2-Cg alkenyl, C3-Cg cycloalkenyl, C,-Cg alkynyl, S(=0)a(C-Cg alkyl),
S(=0)a(C)-Cq haloalkyl), OSO,(C-Cq alkyl), 0SOAC,-Cg haloalkyl), C(=0)H, C(=0)OH, i
C(=0)(C,-Cs alkyl), C(=0)O(C-C alkyl), C(=0)(C;-Cs haloalkyl), C(=0)0(C,-Cy haloalkyl), C(=O)}(C;-C;, cycloalkyl), C(=0)O(C3-Co cycloalkyl), C(=0)C2-C, alkenyl),
C=0)YO(C2-Cs alkenyl), (C-Cg alkyhO(C,-Cg alkyl), (C-Ce alky)S(C,-C alkyl), C(=0)(C,-
Cs alkyDC(=0)O(C-Cy alkyl), phenyl, halophenyl, phenoxy, and Het-1,
or Rg and Ry together can optionally form a 5- to 7-membered saturated or unsaturated cyclic group which may contain one or more heteroatoms selected [rom nitrogen, sulfur, and oxygen, and where said cyclic group can contain >C=0 or >C=S, and where said cyclic group may be substituted with F, C1, Br, I, CN, C-C alkyl, C-Cq haloalkyl, C3-Cs cycloalkyl, C;-Cs halocycloalkyl, C;-Ce cycloalkoxy, C3-Ce halocycloalkoxy, C;-Cs alkoxy,
C-Cé haloalkoxy, (C2-Cg alkenyl, C;-Cs cycloalkenyl, C,-Cq alkynyl, S(=0)(C1-Cq alkyl),
S(=03,(C-Cq haloalkyl), OSO,(C-Cy alkyl), OSO(C,-Cg haloalkyl), C(=0)C;-Cy alkyl),
CE=OO(C-Cq alkyD), C(=0)(C-Cg haloalkyl), C(=0)O(C-Cq haloalkyl), C(=0XCi-Cs cycloalkyl), C=OYX(C;3-Co cycloalkyl), C(=0)(Cy-Cy alkenyl), C(=0)Y(C-C alkenyl), (C-
Cg alkyDO(Cy-Cg alkyl), (C-Cq alkyDS(Cy-Cg alkyl), C(=O)C-Cg alkyDNC(=0YO(C4-Cq alkyl), phenyl, substituted phenyl, phenoxy, and Ilet-1; and ; (k) llet-Tis a 5- or 6-membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur or oxygen. 5
It is understood that in Formula 1, when R2 is H, the compounds may exist in morc than one tautomeric or isomeric lorm, wherein the hydrogen is attached to either of the nitrogen atoms; further, both FE and 7 isomers may exist. Any and all isomeric forms of the compounds of this invention are claimed. : :
In another embodiment Ar, is a substituted phenyl, wherein said substituted phenyl : has one or more substituents independently selected from C;-Cg haloalkyl and C,-Cg haloalkoxy.
In another embodiment Ar is a substituted phenyl, wherein said substituted phenyl has onc or more substituents independently selected from CF, OCF; and OCTHCF;.
In another embodiment Het is selected from triazolyl, imidazolyl, or pyrazolyl, which can be substituted or unsubstituted.
In another embodiment Het is a 1,2,4-triazolyl 10 i
N
~
Ar, 1
Arq N .
In another embodiment Het is 1,4-imidazolyl
N
N / ari” :
In another embodiment Het is 1,3-pyrazolyl
Ary ; ~~ N— 4 ]
Ar, N .
In another embodiment Het is a substituted 1,3-pyrazolyl.
In another embodiment Het is 1,4-pyrazolyl
Ar,
Nef ar”
In another embodiment Ar; is a phenyl. : 5
In another embodiment R1 is H or C-Cg alkyl.
In another embodiment R1 is IT or CH;.
In another embodiment R2 is FH.
In another embodiment R3 is sclected from C,-Cy alkyl, C,-Cq alkenyl, Co-Ce alkynyl,
C1-Cs alkylphenyl, C,-Cg alkylHet-1, C;-Cg alkyl-0-C(=0)C,-Cs alkyl-0-C-Cg alkyl, C)-Cgq alkyl-Q-C(=0)C-Ce alky!-0-C-Cs alkyl-O- C-Cg alkyl, C-Cg alkyl-0-C(=0)C-C, atkyl- 0-C,-Cq haloalkyl, C-Ce alkyl-O-C(=0)C,-Cs alkyl-N(R,)C(=0)-0-phenyl, Cy-Coalkyl-O-
C(=0)(C)-Ce alkyl-N(ROC(=0)-0-C;-Cs alkylphenyl, C,-Ce alkylC(=0IN(R,)C-Cs alkyl,
C-CsalkylC(=0)N(R)C-Cg alkylHet- 1 C(=0)-0-C-Cq alkyl, C;-CealkylC(=OIN(ROC-Cs alkylllet-1, C1-Co alkylC(=O)Tet- 1, C-CoalkylC(=0)N(R)C-Ce alkyI(IN(RO(R)ONC(=0)OH), C}-CpalkylC(=0)N(R)C1-Cs alkyIN(R (Ry), C1-Cs alkylC(=0)N(R CC alkyIN(R)C(=0)-0-C-Cy alkyl, C-Cq alkylC(=0IN(R)C-Cq alkyl(N(R,)C(=0)-0-C-Ce alkyD(C(=0)OH), C)-Cq alkylC(=0)Hel-1C(=0)-0-C-Cg alkyl,
Cy-Co alkyl-O-C(=0)-0-C;-Cy alkyl, C;-Ce alkyl-O-C(=0)C,-Cq alkyl, C-Cealkyl-O-
C(=0)C;5-Cg cycloalkyl, Cy-Cg alkyl-O-C(=O)Het-1, or C}-Cg alkyl-0-C(=0)C;-Cg alkyl-
NRC (=0)-0-C,;-C, alkyl, wherein each alkyl, alkenyl, alkynyl, phenyl, and Iet-1 are optionally substituted with one or more substituents independently selected from F, Cl, Br,
C-Cs alkyl, Cy-Cg haloalkyl, C,-Cg haloalkoxy, S(=0),(C,-Cg alkyl), C(=0)OIL, C(=0)O(C}-
Cs alkyl), phenyl, Si(C-Cg alkyl)s, and S(=0).NRR,.
In another embodiment R4 is phenyl, C;-Cg alkylphenyl, Het-1, or C;-Cg alkyl-O- phenyl, wherein each alkyl, Het-1, and phenyl are optionally substituted with one or more substituents independently selected from F, Cl, NRRy, C,-Cs alkyl, C3-Cg cycloalkyl, Ci-Co haloalkoxy, C(=0)O C,-Cg alkyl, or C;-Cg alkoxy.
In another embodiment RS is substituted with oxo, C(=0)OH, phenyl, and Het-1, wherein each phenyl and Het- 1, may be optionally substituted with one or more substituents independently selected (rom oxo, C-Cg haloalkyl, C-Cg haloalkoxy, C(=0)OH, and halophenyl. :
In another embodiment R, and R, arc independently selected from H and phenyl, wherein said phenyl, may be optionally substituted with one or more substituents independently sclected from F and CI.
In another embodiment:
Ary is a substituted phenyl wherein said substituted phenyl, has one or more ;
C;-Cg haloalkoxy;
Het is a triazolyl;
Ar; is a phenyl;
Rlis TT
R2 is I;
R3 is C-Ce alkylllet-1 wherein said alkyl and IHet-1 are optionally substituted with one or more substituents independently selected [rom ¥, Cl, Br, C-Cq alkyl, C;-Cg haloalkyl, C;-Cs haloalkoxy, S(=0)a(C;-Cy alkyl), C(=0)OIL, C(=0)O(C-Cy alkyl), phenyl,
Si(C-Ce alkyl), and S(=0),NR<Ry;
R4 is phenyl, wherein said phenyl is optionally substituted with onc or more substituents independently selected from F, Cl, NR(R,. C-Cq alkyl, or (C;-Cg alkoxy: and n=0, |,or2; 10) Ri and R, are independently selected (rom H and phenyl, wherein said phenyl, may be optionally substituted with one or more substituents independently selected from F and C1; and
Het-1 is a 5- or 6-membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected [rom nitrogen, sulfur or oxygen.
In another embodiment Het-1 is selected from benzoluranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazoly! cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl. pyridyl, pyrimidinyl, pyrrolyl. quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro- oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[1,3,4]- oxadiazolyl.
In another embodiment Tet is selected benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazoly! cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, : oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydroluranyl, tetrahydropyranyl, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[1,3,4]-oxadiazolyl.
In another embodiment Het-1 is selected from henzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, benzothiadizolyl, cinnolinyl, furanyl, indazolyl, indolyl, imidazoly!, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tctrazolyl, thiazolinyl, thiazolyl, thienyl, thienylpyrazolyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4-tetrahydro- quinolinyl, 4,5-dihydro-oxazolyl, 4.5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3- dihydro-[1,3,4]-oxadiazolyl.
In another embodiment Het-1 is selected from benzothiadizolyl, furanyl, oxazolyl, and thienylpyrazolyl.
While these embodiments have been expressed, other embodiments and combinations of these expressed embodiments and other embodiments are possible.
The Molecules of Formulae One, Two and Three will generally have a molecular mass of about [00 Daltons to about 1200 Daltons. ITowever, it is generally preferred if the molecular mass is from about 120 Daltons to about 900 Daltons, and it is even more 200 generally preferred if the molecular mass is from about 400 Daltons to about 800 Daltons.
PREPARATION OF TRIARYL INTERMEDIATES
Compounds of this invention can be prepared by making a triaryl intermediate, Ar,- flet-Arp, and then linking it to the desired intermediate to form the desired compound. A wide variety of triaryl intermediates can be used to prepare compounds of this invention, provided that such triaryl intermediates contain a suitable functional group on Ar; to which the rest of ; the desired intermediate can be attached. Suitable functional groups include an oxoalky! or a ; formyl group. These triaryl intermediates can be prepared by methods previously described in ; the chemical literature, including Crouse et al. PCT Int. Appl. Publ. WO2009/102736 Al. ;
PREPARATION OF HYDRAZONE-LINKED COMPOUNDS
Hydrazone-linked compounds can be prepared (rom the corresponding aryl aldehydes or ketones by one of three methods: (1) by reaction with a hydrazine, followed by reaction with an aryl isothiocyanate in tetrahydrofuran (THI), at temperatures between () and 100 °C 14 i
(Reaction A); (2) by reaction with methyl hydrazinecarbodithioate, followed by reaction with an aniline in a polar aprotic solvent such as NN-dimethyllormamide (DMI), at temperatures between 25 and 150 °C (Reaction BY; or (3) by reaction with an aryl thiosemicarbazide, that is either commercially available or can be prepared by one who is skilled in the art, in a polar protic solvent such as ethyl alcohol (TitO11), at temperatures between and [00 °C (Reaction
QO).
I. NH,NH-R2 eee (A) 2. R4-NCS,
THE, 0 - 100 °C 3 RI R2 R3 % TAN He hd : “NTS > x 2 3. : ag 0 Lh WASNT ©) 2. R4-NH,. DMF. 5 25-150°C
S
©
HN A Ro
Hogs
EtOH, 0-100 °C
PREPARATION OF ALKYLATED HYDRAZONE-LINKED COMPOUNDS
Alkylated hydrazone-linked compounds can be prepared from the corresponding hydrazonc-linked compounds by one of two methods: (1) by reaction with an alkylating agent in ELOH or acelone, at temperatures between () and 100 °C for from 1 to 24 h or (2) by : reaction with an alkylating agent in chloroform (CHCl3), dichloromethane (CH,Cly), or other halocarbon solvent, with or without a base such as sodium bicarbonate, at from 20) to 60 °C.
Alkylating agent,
EtOH -— (D) 0-100 °C, 1-24 h Rl R2
RI R2 R3 Het, N,N
IN I Af} AG Np TP py
Het, Nz Ni. S
AT) 2 r Rd Alkylating RS agent,
CH,Cl, or
CHCl, 20-60 °C, 1-24 h
Compounds of Formula Two, wherein R5 forms a ring with Nj (see Scheme below) or of Formula Three, wherein R35 forms a ring with N3, can be prepared from a suitable acyclic precursor by using a-halo acids, acid halides, esters, or ketones (F or G or H). For example, treatment of the thiosemicarbazone with a slight excess of an o-halo ester, in a : protic solvent such as EtOH or methyl alcohol (CH;O!H) results in S-alkylation and subsequent ring closure exclusively onto Nj (Reaction F; see for example, J. Indian Chemical :
Society 1966, 43, 275-276, or J. Heterocycl. Chem. 1978, 15, 335-336). When an aprotic solvent such as CHCl; or dichloroethane (CICIT;CH,CI) is used at temperatures from 30 °C : to 80 °C, the orientation of addition of o halo ketones also favors closure onto Nj, with ; subsequent dehydration to form an imino thiazoline (Reaction GG). With o-halo acids or acid halides or esters in a halocarbon solvent such as CH,Clp or CICH,CH,Cl, ring closure onto both Nz (Reaction H) and Nj is observed. Though these reactions often proceed in the absence of added base, a base such as sodium bicarbonate, sodium carbonate or sodium ; acetate, or an amine base such as pyridine or tricthylamine, can be added. 16 1
Br._CO,H & RY —_— RB fet _ x Nj Ns 0 (F)
Br coc, AT TAT NEL 2 2
R RZ R EOI or MeOf
Het ~Nay Nj
AAR NTE TR LL Loi r : } 3
Ara SN, AS (G) — S
Br._CO,Cll; R —_— N? ! . rR! 3 .
CH,Cl, or 7~S (Dh
Het __ Js Ny g
Ary Al N;
CICH,CH, Cl ) “ = O i
Alternatively, 3-arylidineimino-2-aryliminothiazolin-4-ones can be prepared by : treating an aldehyde or ketone, wherein R1 is as previously described, with a 3-amino- 2- (arylimino)thiazolidin-4-one in acetic acid at from 30) to 70 °C as shown in the following scheme (I). The intermediate 1-amino-2-aryliminothiazolin-5-one, wherein R4 is phenyl, has been described (see for example, J. Org. Chem. 1962, 27, 2878); it was prepared in 80% yicld by treatment of 4-phenyl thiosemicarbazide with ethyl 2-chloroacetate and sodium acetate in hot EtOFL 0
H H Br _ CO,CH; ham
S
NTS Mey ———— = ENT
S N
R4
Ar Ars ~~ < RI :
Hef YY M 0 0 :
R1 et Ty
Af Ag NOY
N
~R4
Alternatively, compounds of Formula 2 and Formula 3 may be formed by heating a thiosemicarbazone precursor with a di-halo group Hall-R5-Hal2 such as |-bromo-2-chloro ethane or diiodomethane, in acetone or 2-butanone or other suitable solvent, using a base such as potassium carbonate or tricthylamine, at temperatures between ambient and 100 °C for from 1 to 72 hours. The S-alkylated intermediate undergoes cyclization at N2 or N3 to generate compounds of Formula Two or Formula Three (Reaction J). In some cases, addition ol KI may be required to accelerate the cyclization of the intermediate S-alkylated derivatives to the ring-closed products.
Hal Hal
R1 Ngo RE al
Het H H RS let PN S ~ a .N.__N : oN N ~R7
Af) XEON YY Cre T= An An N Y ’ . S N.
R4
Kl hh
Rl Rs Ri
Het / NL. Het PN N S
N S 7 - :
Af NN Ny Af, AY N 7 Ne.
N N—
Rd RA
An alternative method of preparing compounds of this invention is by treatment of a thiosemicarbazone precursor with an unsaturated ester or acid chloride (Reaction L).
R*
N.
O Het SPL
Ary” Ar, Nj 2
R' RZ RY Ci o (L) 1 E
Het, A Na Ns —
Ari~ © “Af, NU ge s"\
Het x Ra 0 _ e a . A :
Ary” “Ar, Nj 2 Ry :
Substituted hydrazinecarbothioamide intermediates, such as those utilized in Method
C above, can be prepared by a number methods known in the chemical literature.
Alternatively, compounds wherein R,, Ry. and R, are not derived from a comunercially : available aniline can be prepared according to the scheme below. For example, a 2-halo nitrobenzene, such as 2-bromonitrobenzene, substituted with one or multiple R substituents, : wherein R. can be FH, alkyl, alkoxy, or halo, such as fluoro, can be reacted with a boronic acid or haronate ester, such as the substituted 4,4,5,5-tetramethyl-1,3,2-dioxaborolane, wherein R, and R,, are [1, in the presence of a base, for example sodium carbonate, and a palladium catalyst, such as bis(triphenylphosphine)palladium(Il)chloride, in an aqueous solvent system, such as 4:1 dioxane / walter, at an elevated temperature, for example 80 °C, affords the olefinic substituted nitrobenzene compounds. Alternatively, R, and R,, can be taken together to form a ring, such as a cyclopentene, to give the corresponding 2-(cyclopent-1-en-1-yl)- 4.4.5,5-tetramethyl-1,3,2-dioxaborolane, which under the conditions described above affords the cyclic alkene substituted nitrobenzene. Treatment a solution of the olefinic nitrobenzenes in an aprotic solvent, such as ethyl acetate, wherein Ra, Rp, and Re are as defined above, with hydrogen gas in the presence of a catalyst, for example palladium on carbon (Pd/C), affords the corresponding alkyl or cycloalkyl substituted anilines. Treating a biphasic solution of the anilines, wherein R,, Ry, and R, are as defined, in a mixture of halogenated solvent and water, such as 2:1 dichloromethane /water, with a hase, such as sodium hydrogencarbonate, followed by thiophosgene affords the intermediate isothiocyanatobenzenes. Separation of the phases, followed by drying and evaporation of the organic solvent affords the crude intermediate which is immediately dissolved in an alcohol, such as ethanol, and treated with hydrazine hydrate to give the hydrazinecarbothioamide intermediates, wherein R,, Rp, and R. are as defined. 0.4.0 Ty Lor 0 UR R, 5
N rn Toke OK ot NH, Lod
NB eee ~ Ry, —» ~ Ry _—
CY es | jv 2) NHa=Nily
R. R, Re ¥ (M)
HN A R,
H SN Ry, “R,
EXAMPLES
The examples arc for illustration purposes and are not to be construed as limiting the : invention disclosed in this document to only the embodiments disclosed in these examples.
Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Scal™ from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover
Unimelt capillary melting point apparatus or an OptiMclt Automated Melting Point System from Stanford Research Systems and are uncorrected. Molecules are given their known names, named according to naming programs within MDL ISISTM/Draw 2.5, ChemBioDraw
Ultra 12.0 or ACD Name Pro. [f such programs are unable to name a molecule, the molecule is named using conventional naming rules. 'H NMR spectral data are in ppm (8) and were recorded at 300, 400 or 600 MHz, and “C NMR spectral data are in ppm (8) and were recorded at 75, 100 or 150 MHz, unless otherwise stated.
Example 1: Preparation of (F)-NV-(4-dimethylamino)pheny!)-2-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene )hydrazine-carbothioamide (Compound I-1) [Synthesis Method A].
LS
OAT S Ql. 1s Fr =
Step 1. (I2)-3-(4-(Hydrazonomethyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H- 1,2,4-triazole. To a 250 milliliter (mL) round-bottomed flask containing hydrazine hydrate (64% aqueous (aq) solution; 7.27 ml, 15.0 millimoles (mmol) in EtOH (100 mL) at 80 °C was added 4-[1-(4-trifluoromethoxyphenyl)- 1H-[1,2,4]triazol-3-yl}-benzaldehyde (5.00 ; grams (g), 1.50 mmol) portionwise over 5 minutes (min). The solution was stirred at reflux for an additional 3 hours (h) before being diluted with water (H,0; 300 mL) and cooled to 0) °C. The precipitated product was collected by vacuum filtration as a white solid (4.89 g, 93%): mp 222 — 226 °C; 'H NMR (400 MHz, DMSO-ds) 5 8.59 (5, 1H), 8.22 (d, J=8.2 Hy, 235 2H), 7.834-7.79 (m, 3H), 7.66 (d, J = 8.3 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.29 (s, LH), 5.63 (brs, 21); ESIMS m/z 348 (M+).
Step 2. To a 25 mL round-bottomed flask containing (EY-3-(4-(hydrazonomethyl)- phenyl)- I-(4-(tritluoromethoxy)phenyl)- | H-1,2,d-triazole (250 mg, 0.720 mmol) in THI? (10 : ml.) was added 4-isothiocyanato-N,N-dimethylaniline (385 mg, 2.16 mmol). The contents were heated at 65 °C with stirring for 2 h before the solvent was removed under reduced pressure, The residue was slurried in CH,Cl (10 ml) resulting in precipitation ol product material. The desired product was obtained as a yellow solid via vacuum filtration (350) mg, 20 i
93%): mp 205 — 208 °C; "11 NMR (400 Miz, DMSO-dg) 3 11.78 (s, LI), 10.02 (s, 111), 9.42 (s, LHD, 8.19-7.99 (m, 61), 7.64 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.3 Hz, 21), 7.73 (d, / = 8.3
Hz, 211), 2.92 (s, 611); ESIMS m/z 526 (M+11).
Example 2: Preparation of N-(3-(dimethylamino)phenyl)-2-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yhbenzylidene)hydrazinecarbothioamide (Compound 1-2) [Synthesis Method B]. 0 NNN /
AOU
Step 1. (E)-Methyl 2-(4-(1-(4-(trifluoromethoxy)pheny!)-1H-1,2 4-triazol-3- yhbenzylidene)hydrazinecarbodithioate. ‘To a 250 ml. round-bottom flask containing hydrazinecarbodithioic acid methyl ester (2.38 g, 1.95 mmol) in EtOH (100 mL) was added 4-[ 1-(4-trifluoromethoxyphenyl)- L H-[ 1,2 4 |triazol-3-yl]-benzaldehyde (5.00 g, 1.50 mmol). :
The vessel was heated at 80 °C for 3 h before being diluted with H;0 (300 mL) and cooled to 0 °C. The precipitated product was collected by vacuum filtration as an off-white solid (6.13 g, 93%): mp 204 — 206 °C; 'H NMR (400 MHz, DMSO-dg) § 13.39 (s, 11), 9.43 (s, 11D), 8.38 (s, 1H), 8.21 (d, J = 8.3 Hz, 2H), 8.09 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H), 7.62 (d, J =8.3 lz, 2ID), 2.57 (s, 311); ESIMS m/z 438 (M+11).
Step 2. To a 50 ml. round-bottomed flask containing (F)-mcthy! 2-(4-(1-(4- (trifluoromethoxy)phenyl)-1 H-1,2 4-triazol-3-yl)benzylidene)hydrazinecarbodithioate (250 mg, 0.571 mmol) in DMF (3 ml.) was added N1,N1-dimethylbenzene-1,3-diamine (195 mg, 1.43 mmol). The contents were heated at 150 °C with stirring for 5 h before the solution was allowed to cool overnight. The mixture was filtered, and the filtrate was purified via RP-
HPLC to afford the desired material (235 mg. 78%) as an off-white solid: mp 192 — 194°C; : 'H NMR (400 MHz, DMSO-dg) 8 11.82 (s, 11), 10.04 (s, 1H), 9.41 (s, LTD), 8.19 (5, 1H), 8.16-7.99 (m, 6H), 7.61 (d, J = 8.3 Hz, 2H), 7.16 (t, J = 7.2 Hz, 1H), 7.01 (m, 1H), 6.87 (m,
LH), 6.58 (m, LH), 2.88 (s, 6H); ESIMS m/z 526 (IM+H]|"). :
Example 3: Preparation of N-benzyl-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4- triazol-3-yl)benzylidene)hydrazinecarbothioamide (Compound I-3) [Synthesis Method
Cl.
Fo LO 1 oO
NN NN
WO
To a 50 mL. round-bottomed flask containing 4-[ 1-[4-(trifluoromethoxy)phenyl]- 1,2 4-triazol-3-yl]benzaldehyde (500 mg, 1.5 mmol) in EtOH (3 mL) was added 4- benzylthiosemicarbazide (650 mg, 3.6 mmol). The reaction mixture was heated at 80 °C overnight. HQ was added upon completion of the reaction, and the crude product material was isolated by vacuum filtration. The title compound was isolated via RP-HPLC as a white solid (390 mg, 52%): mp 220-224 °C; 'H NMR (400 MHz, CDCl3) § 9.29 (s, 1H), 8.59 (s, 1D), 8.21 (d, J=8.4 Hz, 2H, 7.85-7.79 (m, 3H), 7.71 (d, J = 8.4 Hz, 2H), 7.46-7.30) (m, SI), 5.01 (d. J =5.8 Hz, 2H); ESIMS m/z 497.2 (M+H).
Compounds 1-4 through 1-31 in Table 1 were synthesized in accordance with the examples above. Other intermediates used in the preparation of compounds of this invention were prepared in accordance with the procedures described in Brown, et al, WO 2011017504
Al, or by other known routes.
Example 4: Preparation of N-(4-dimethylaminophenyl)-S-methyl-2-{4-[1-(4- trifluoromethoxyphenyl)-1H-[1,2,4]-triazol-3-yl}-benzylidene}-hydrazine- carbothioamide (Compound 1C) (Synthesis Method D)
E « 4
Oh 0 ag
N
A solution containing (F)-N-(4-(dimethylamino)pheny!)-2-(4-(1-(4- (trifluoromethoxy)-phenyl)- | H-1,2,4-triazol-3-yhbenzylidene)hydrazinecarbothioamide (150 mg, 0.285 mmol) and iodomethane (0.054 ml., 0.856 mmol) in EtOH (5 ml.) was heated at 80 °C for 3 h before the solvent was removed under reduced pressure. The residue was purified via normal phase flash chromatography (gradient elution with hexanes/TtOAc) to afford the title compound as an orange foam (93 milligrams (mg), 60%): 'H NMR (400 22 L
MTiz, DMSO-de) 8 8.61 (s, 1H), 8.48 (s, 1H), 8.22 (d, J = 8.24 Hz, 2H), 8.17 (s, ITI), 7.89 (d,
J=82411z. 211), 7.80 (d, J = 8.28 Hz, 21D), 7.41 (d, J = 8.28 Hz, 2H), 7.19 (d, J = 8.24 lz. 2M), 6.71 (d, J = 8.24 [z, 21), 2.99 (s, 611), 2.42 (s, 3H); FIMS m/z 540 (M™).
Example 5: General procedure for S-alkylation of triaryl thiosemicarbazones (Synthesis Method E)
A stirred solution of the thiosemicarbazone and alkylating reagent in CH,Cl, or chloroform (CHCl) was heated at from 35 to 50 °C for from 10) 10 24 h. The cooled solution : was concentrated under reduced pressure. The residue was generally purified via : 10 chromatography using a chloroform/methanol (CHCL;/CH;OH) or EtOAc-hexane solution as the eluent to afford the S-alkylated products.
Example 6: Preparation of (S)-tert-butyl 3-((2-((£)-(2,6-dimethylphenylimino)-((£)-2-(4- (1-(4-(trifluoromethoxy)phenyh)-1H-1,2 4-triazol-3-yl)benzylidene)hydrazinyl)-
I5 methylthio)acetamido)methylpiperidine-1-carboxylate (Compound 56C) (Synthesis
Method E) 0 70 P
C) NL ~~
H S
F_O =N 0x ANNI
NY O
To a solution of bromoacety! bromide (26 microliters (pL), 0.299 mmol) in dichloroethane (3 ml.) was added dropwise a solution of ($)-rert-butyl 3- (aminomethyDpiperidine-1-carboxylate (63.9 mg, 0.298 mmol) in dichloromethane (1 mL), : followed by N-ethyl-N-isopropylpropan-2-amine (76 mg, 0.588 mmol). This mixture was stirred al room temperature for 30) min, then (E)-N-(2,6-dimethylphenyl)-2-(4-(1-(4- : (trifluoromethoxy)phenyl)- 1 H-1 ,2.4-triazol-3-yhbenzylidene)hydrazine-carbothioamide (100 ; mg, 0.196 mmol) was added as a solid and the mixture was heated to 40 °C for 90 min. Tt was then allowed to cool to room temperature and evaporated under reduced pressure, giving a : light yellow glass, which was dissolved in acetonitrile (2 ml.) and allowed to stand at room temperature. The resulting precipitate was isolated by centrifuge and decanting, washing with {
fresh acetonitrile. The solid was dried under a nitrogen stream and then under high vacuum. ‘The crude product was recrystallized from acetone-isopropyl alcohol. The title compound was isolated as a white solid (36.5 mg. 24%): mp 148 — 151 °C; "FI NMR (400 MHz, methanol-dy) 8 9.18 (s, 111), 8.59 (s, 111), 8.30 (d, J = 8.1 Hz, 21D), 8.12 (im, 211), 8.07 - 8.00 (m,2H), 7.38 -7.43 (mm, 2H), 7.33 (dd, J = 8.6, 6.5 Hz, 1H), 7.25 (d, J = 7.6 Hz, 2H), 4.02 (m, 210), 3.97 — 3.75 (m, 21), 3.21 (d, J = 6.9 [1z, 211), 2.90 (m, 11D), 2.59 (m, LID), 2.35 (s, 6H), 1.84 (m, 2H), 1.78 — 1.63 (m, 2H), 1.44 (5, 9), 1.29 (im, 3H); ESIMS m/z 765 (M+H). :
Example 7: Preparation of (17,2F)-2-0x0-2-(((R)-piperidin-3-ylmethyl)amino)ethy! V- (2,6-dimethylphenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2.4-triazol-3- yhbenzylidene)hydrazinecarbimidothioate trifluoroacetic acid (Compound 62C) (Synthesis Method K)
CF,CO,H ( 0
Oa
FA Noy 0
A solution of (§)-rert-butyl 3-((2-((£)-(2,6-dimethylphenylimino)-((E)-2-(4-(1-(4- (triflucromethoxy)phenyl)- 1H-1,2 4-triazol-3-yl)benzylidene)hydrazinyDmethylthio)- acetamido)methyl)piperidine-1-carboxylate (32.0 mg, 0.042 mmol) in TFA (250 ul, 3.24 20° mmol) was stirred at room temperature for 10 min. EO (10 ml) was then added giving a white precipitate, which was isolated by centrifuge and decanting, then rinsing with fresh
Et;0 (5 ml). The solid was dried under nitrogen stream and then under high vacuum giving the title compound as a white solid (19.8 mg, 60%): mp 110 — 120 °C; '"H NMR (400 MHz, methanol-dy) 8 9.18 (s, 1H), 8.56 (m, 111), 8.26 (m, 211), 8.16 — 7.84 (m, 411), 7.52 (m, 2[1), 7.27 (m, 1H), 7.22 (m, 2H), 4.00 (s, 2H), 3.28 (m, 3H), 3.06 - 2.83 (m, 1H), 2.75 (t, J = 12.2 ;
Hz, 111), 2.34 (s, 611), 2.21 — 1.83 (m, 411), 1.72 (m, LI), 1.47 — 1.19 (m, 2H); ESIMS m/z 665 (M~+H).
Example 8: Preparation of 2-(((Z)-((4-methoxy-2,6-dimethylphenyl)imino)((F)-2-(4-(1- :
(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidenejhydrazinyl)methy!)- thio)acetic acid sodium salt (Compound 68C)
O0— wo 0
FO J
+L N-NH
F VN) <n
To a solution of 2-((Z)-(4-methoxy-2,6-dimethylphenylimino)((F)-2-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2 4-triazol-3-yl)benzylideneYhydrazinylmethylthio)acetic acid (77.7 mg, 0.130 mmol) in THF (10 ml.) was added slowly sodium methanolate (0.5 M in methanol; 260 ul, 0.130 mmol) at room temperature. The mixture immediately turned a darker yellow and was then evaporated at room temperature under vacuum giving a light orange solid. This material was triturated with E20 (2X) and isolated by decanting using a centrifuge and drying under a nitrogen stream and then under high vacuum. The title compound was isolated as a light orange solid (32 mg, 39%). mp 146 — 154 °C; '"H NMR (400 MTiz, methanol-dy) 6 9.11 (s, 1H), 8.64 — 7.68 (m, 711), 7.51 (m, 2H), 6.70 (s, 2H), 3.85 ~3.70(m, 4H), 3.61 (m, 1H), 2.29 (s, 6H); ESIMS m/z 599 (M+H).
Example 9: Preparation of (Z)-3-(4-methoxy-2,6-dimethylphenyl)-2-((F)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-4- one (Compound 69C) (Synthesis Method F)
FAO 0
QF
N-N "a oo
LO
0—
To a solution of (K£)-N-(4-methoxy-2,6-dimethylphenyl)-2-(4-(1-(4- (trilluoromethoxy)phenyl)- 1 H-1,2,4-triazol-3-ybenzylidene)hydrazine-carbothioamide (250) ; mg. 0.462 mmol) in EtOH (5 mL) was added methy] bromoacetate (100 mg, 0.65 mmol), and ]
the mixture was heated to 70 °C for 4 h. The mixture was allowed to cool to room temperature and diluted with walter (1 mL). The precipitate was vacuum filtered, giving the title compound as a white solid (204 mg, 76%): mp 188 - 190 °C; 'H NMR (400 MFlz,
CDCl3) § 8.56 (s, 1H), 8.33 (s, 1H), 8.22 (d, J = 8.1 Hz, 2H), 7.90 - 7.70 (mm, 4H), 7.39 (d, J = 87107, 21D, 6.72 (s, 211), 4.01 (s, 211), 3.87 — 3.73 (s, 31D), 2.18 (s, 611); ESIMS m/z 581 (M+),
Example 10: Preparation of 4-((27)-3-(2,6-dimethylphenyl)-2-((4-{1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazono)-2,3- dihydrothiazol-4-yl)-N,N-diethylaniline (Compound 74C) (Synthesis Method G)
Fo —
F 0 SI "
N
Bo
N 7 :
To a solution of (F:)-N-(2,6-dimethylpheny!)-2-(4-( | -(4-(trifluoromethoxy)phenyl)- 11-1,2 4-triazol-3-yl)benzylidene)hydrazine-carbothioamide (74.7 mg, 0.144 mmol) in dichloroethane (5 ml), was added a-bromo-4-dicthylamino)acetophenone (53.9 mg, 0.199 mmol), and the mixture was heated to 40) °C for 4 h. The mixture was then cooled to room temperature and evaporated under vacuum. The crude material was triturated with acetonitrile : and decanted (2X). The resulting solid was dried under a stream of nitrogen, giving the title compound as a pale yellow solid (25 mg, 25%): mp 190 — 193 °C dec; 'H NMR (400 MHz, : methanol-dy) 6 9.20 (s, 1H), 8.38 (s, 1H), 8.31 — 8.24 (m, 2H), 8.08 — 8.00 (im, 2H), 7.95 — 7.88 (m, 2H), 7.55 — 7.48 (m, 311), 7.48 — 7.36 (m, 5H), 7.31 (d, J =7.7 Hz, 2H), 3.60 (q, J = 7.2 Hz, 411), 2.20 (s, 61), 1.07 (t, J = 7.2 Hz, 611); ESIMS m/7 632 (M+H).
Example 11: Preparation of (Z)-2-(2,6-dimethylphenylimino)-3-((})-4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylideneamino)thiazolidin-4-one (Compound 81C) (Synthesis Method I)
TU pd ~ be,
To a solution of 1-(2,6-dimethylphenylthiourea (1.0 g, 5.55 mmol) in EtOH (10 ml.) was added methyl 2-bromoacetate (1.0 g, 6.5 mmol) and sodium acetate (1.0 g, 12.2 mmol).
The solution was stirred and heated to reflux for | h, then it was cooled and the liquid was decanted from a small amount of solid material and the liquid was then diluted with water (10 ml.). The precipitate was isolated by [filtration to give (1.1 g, 83%) of (7)-3-amino-2-(2,6- dimethylphenylimino)thiazolidin-4-one: mp 149 — 152 °C; 'H NMR (400 Miz, CDCl) 8 7.06 (d, J =7.2 Hz, 2H), 6.98 (m, 1H), 4.75 (s, 2H), 3.80 (s, 2H), 2.12 (s, 6H); ESIMS m/z 236 (M+1).
A portion of this material (0.07 g. 0.3 mmol) was dissolved in glacial acetic acid (3 mL) and treated with 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2 4-triazol-3-yl)benzaldehyde (0.10 g, 0.30 mmol), and the solution was heated to 60 °C for 2 h. The solution was then cooled and diluted with water (1 mL), and the resulting solid was filtered and air-dried to give the title compound (0.12 g, 67%): mp 209 - 213 °C; "H NMR (400 MHz, CDCl3) § 9.42 (s, 1H), 8.59 (s, 1H), 8.28 (d, J = 8.4 Hz, 2H), 8.01 (d, J = 8.3 Hz, 2H), 7.80 — 7.77 (m, 2H), 7.43 =7.34 (m, 2H), 7.07 (d, J = 7.5 Hz, 2), 6.98 (dd, J = 8.2, 6.7 Hz, 1H), 3.90 (s, 2H), : 2.17 (s, 6H); ESIMS m/z 551 (M+H).
Example 12: Preparation of (2Z,NE)-2-((2-isopropylphenyl)imino)-N-(4-(1-(4- : (triflucromethyl)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)-1,3-thiazinan-3-aminc and (Z2)-3- (2-isopropylphenyl)-2-((F)-(4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3- yhbenzylidenc)hydrazono)-1,3-thiazinane (Compound 87C and 179C) (Synthesis Method » /=N £ on I)
Fr J J A
To (E)-N-(2-isopropylphenyl)-2-(4-( 1-(4-(trifluoromethyl)phenyl)- 1T- 1,2 4-triazol-3- yhbenzylidene)hydrazinecarbothioamide (200 mg, 0.393 mmol) and potassium carbonate (217 mg, 1.57 mmol) in butanone (10 ml) in a 25 ml. vial equipped with a stir bar and vigruex column was added [-hromo-3-chloropropane (0.047 ml, ).472 numol). The reaction was heated to 60 °C overnight. The reaction was determined to be complete by LCMS. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was : extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided two compounds. The minor compound was dried overnight under house vacuum providing the title compound 8§7C (2ZNE)-2-((2-isopropylphenyl)iniino)-N-(4-(1-(4-(trifluoromethylphenyl)-1 H-1,2 4-triazol- 3-yl)benzylidene)-1,3-thiazinan-3-amine (28.5 mg, 13%) as a yellow solid: mp 187-189 °C; "H NMR (400 MHz, CDCl;) 3 8.81 (s, 1H), 8.66 (s, 1H), 8.21 (d, J = 8.3 Hz, 2H), 7.92 (d, J =8.4 Hz, 2H), 7.81 (t, J = 10.2 Hz, 4H), 7.30 — 7.26 (m, 2H), 7.17 = 7.04 (m, 11), 6.83 (d, J =6.4 Hz, 1H), 3.96 (t, J = 6.1 Hz, 2H), 3.13 (heptet, J = 6.9 Hz, 1H), 2.97 - 2.90 (m, 2H), 247-238 (m, 2H), 1.25 (d, J =7.5 Hz, 6H); ESIMS m/z 550 (M+H). The major compound was recrystallized with MeOH. The solid was filtered, washed with MeOH and dried at 50°C under vacuum. The solid was then azeotroped with acetone (3x) and the resultant solid was : dried at 50°C under vacuum providing the title compound 179C (Z)-3-(2-isopropylphenyl)-2- ((E)-(4-(1-(4-(triflTuoromethyl)phenyl)- 1 H-1,2 4-triazol-3-yl)benzylidene)hydrazono)-1,3- thiazinanc as a yellow solid (92.3 mg, 0.168 mmol, 43%): mp 212-213 °C; '"H NMR (400
MHz, CDCl3) 8 8.64 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.06 (s, 1H), 7.91 (d, J = 8.5 Hz, 2H), 7.79, J=8.6 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.38 (dd, J = 7.8, 1.6 Hz, 111), 7.33 (td, J = 7.5, 1.4 Hz, 1H), 7.29 - 7.23 (m, 1H), 7.18 (dd, J = 7.8, 1.4 Hz, 1H), 3.78 ~ 3.72 (m, 1H), 3.59 -3.48 (m, LHD), 3.18 — 3.04 (m, 31D), 2.40 - 2.30 (m, 21D), 1.26 — 1.20 (m, 611); ESIMS m/z 550 (M+H).
Example 13: Preparation of (Z)-3-(2-cyclopropylphenyl)-5-methyl-2-((E)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidin-4- one (Compound 127C) (Synthesis Method F) .
/=N
Cd
So re
To (E)-N-(2-cyclopropylphenyl)-2-(4-( 1-(4-(trifluoromethoxy)phenyl)- L H-1,2 4- triazol-3-yhbenzylideneyhydrazinecarbothioamide (100 mg, 0.191 mmol) and sodium acetate (63.0 mg, 0.765 mmol) in LOI (4 mL) was added methyl 2-bromopropanoate (0.026 ml, 0.230 mmol). The reaction was heated to 60 °C overnight. The reaction was then heated to 85 °C for 72 hours. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by {lash column chromatography provided the title compound as a white solid (32.5 mg, 0.056 mmol, 30%): mp 112 — 115°C; "TI NMR (400
MHz, CDCl3) § 8.58 (s, 1H), 8.32 (s, LH), 8.22 (d, J = 8.3 Hz, 2H), 7.87 -= 7.75 (m, 4H), 7.43 —7.32 (m, 4H), 7.26 - 7.24 (m, 211), 4.23 (q, J = 7.3 Hz, 1H), 1.85 - 1.78 (m, 4H), 0.90 ~ 0.78 (m, 2H), 0.78 — 0.69 (m, 1H), 0.65 — 0.55 (m, 1H); ESIMS n/z 578 (M+H).
Example 14: Preparation of (7)-3-(2-isopropylphenyl)-2-((E)-(4-(1-(4- (trifluoromethoxy)phenyl)-1#-1,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidine {Compound 132C) (Synthesis Method J) i.
Fo z eo ;
To (E)-N-(2-isopropylphenyl)-2-(4-( 1-(4-(tri [tuoromethoxy)phenyl)-1H-1,2,4-triazol- 3-yhbenzylidene)hydrazinecarbothioamide (214 mg. 0.407 mmol) and potassium carbonate (225 mg, 1.63 mmol) in butanonc (4 ml) was added 1-bromo-2-chloroethane (70.0 mg, 0.489 mmol). The reaction was heated to 90 °C overnight. The reaction was determined 10 be complete by LCMS. The reaction mixture was cooled, diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were filtered through i a phase separator and concentrated. Separation by flash column chromatography and drying the recovered solid at 55 °C under vacuum provided the title compound as a white solid (137 mg, 0.249 mmol, 61%): mp 193 - 196 °C; 'H NMR (400 Ml iz, CDCl3) 8 8.56 (s, 1H), 8.22 (s, LHD, 8.17 (d, J = 8.4 Hz, 2H), 7.80 (ddd, J = 9.53, 6.9, 4.9 Hz, 4H), 7.43 — 7.33 (m, 4H), 731-721 (m, 2H), 4.050d, J=9.4,7.1 Hz, HD), 3.97 - 3.87 (m, 110), 3.42 —= 3.33 (m, LH), 3.33 -3.24 (m, 1H), 3.12 (heptet, J = 6.8 Hz, 1H), 1.27 (d, J = 6.8 Hz, 3H), 1.22 (d, 7=6.9 17, 311); ESIMS mn/; 552 (M+H).
Example 15: Preparation of (Z)-3-(2-isopropylphenyl)-4-methyl-2-((F)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazono)thiazolidine (Compound 155C) (Synthesis Method J) a
F ‘NZ S 30 Cl
To (E)-N-(2-isopropylpheny!)-2-(4-(1-(4-(trilluoromethoxy)phenyl)- LH-1,2 4-triazol- 3-yhbenzylidene)hydrazinecarbothioamide (300 mg, 0.572 mmol) and potassium carbonate (316 mg, 2.29 mmol) in butanone (4 ml) was added 1,2-dibromopropane (0.072 ml, 0.686 mmol). The reaction was heated to 85 °C overnight. The reaction was determined to be complete by LCMS. The reaction mixture was diluted with DCM and washed with water.
The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by {lash column chromatography provided a yellow solid. The solid was recrystallized from MeOH. The solid was filtered, washed with MeOH, and dried to provide the title compound as a yellow solid which was dissolved in acetone and concentrated (3x). The light yellow solid was collected and dried under to provide the title compound as a 1:1 mixture of rotational diastercoisomers (75.1 mg. 0.133 mmol, 23%): mp 201 — 204 °C; 'H NMR of mixture (400 Mllz, CDCl3) § 8.56 (s, 2H), 8.18 (dd, / = 10.8, 7.4
Hz, 6H), 7.84 — 7.73 (m, 8H), 7.45 — 7.30 (m, 8H), 7.30 - 7.23 (m, 2H), 7.20 (d, J = 6.7 Hz,
LH), 7.12 (dd, J = 7.8, 1.2 Hz, 1H), 4.43 — 4.33 (m, LH), 4.16 (dd, J = 12.6, 6.3 Hz, LI), 3.48 i (dt, J=13.3, 6.7 Hz, 1H), 3.37 (dd, J = 10.8, 6.2 Hz, 1H), 3.24 (dt, J = 13.7, 6.9 Hz, | H), 3.08 -2.92 (m, 3H), 1.33 — 1.16 (m, 18ID); ESIMS m/z 566 (M+11).
:
Example 16: Preparation of (Z)-3-(2,6-dimethylphenyl)-4-methyl-2-((K)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazono)-2,3- dihydrothiazole (Compound 173C) (Synthesis Method G)
FT [= s
Lr TO
To a solution of (E)-N-(o-toly!)-2-(4-(1-(4-(trifluoromethoxy)phenyl)- 1 H-1,2,4-triazol-3- yhbenzylidene)hydrazinecarbothioamide (257 mg, 0.520 mmol) in butanone (5 mL) was added triethylamine (0.14 ml., 1.0 mmol) and chloroacetone (0.06 ml, 0.73 mmol) and refluxed at 75 °C for 15 h. The mixture was allowed to cool to room temperature and then transferred to a separatory funnel containing water (5 mL) and extracted twice with dichloromethane. The organic layers were filtered through a phase separator, adsorbed onto silica gel, and purified by flash column chromatography to afford the title compound as a yellow solid (229 mg, 83%): mp 87 °C (dec); 'H NMR (400 MHz, CDCl3) 8 8.56 (s. IHD), 8.19-8.15 (m, 3H), 7.82 — 7.75 (m, 4H), 7.43 —~ 7.30 (m, 5H), 7.24 (d, J = 7.3 Hz, 111), 5.88 (d, J=1.3 Hz, IH), 2.21 (s, 3H), 1.80 (d, J = 1.2 Hz, 311); ESIMS m/; 536 (M+). ;
Example 17: Preparation of (Z)-3-(2-isopropylphenyl)-5-methyl-2-((I7)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazono)-1,3-thiazinane (Compound 178C) (Synthesis Method J) /=N
LOL
Fo z Nn }
To (E)-N-(2-isopropylphenyl)-2-(4-( 1-(4-(trifluoromethoxy)phenyl)- 1 H-1,2 4-triazol- 3-yhbenzylidene)hydrazinecarbothioamide (100) mg, ().191 mmol) and potassium carbonate : (105 mg, 0.763 mmol) in butanone (4 ml) was added I-bromo-3-chloro-2-methylpropane : (39.0 mg, 0.229 mmol). The reaction was heated to 80 °C overnight. The reaction mixture 31 was then diluted with DCM and washed with water. The aqueous layer was extracted with
DCM. The organic layers were poured through a phase separator and concentrated.
Purification by flash column chromatography provided the title compound as a light yellow solid as a mixture of rotational diastereoisomers: mp 186 — 190 °C; "H NMR (400 MHz.
CDCl) 68.55 (d, J=3.611z, 1D), 8.14 (d, J = 8.4 Hy, 2ID), 8.06 (s, 11), 7.84 — 7.77 (m, 211), 7.74(d, J =8.4 Hz, 2H), 7.38 (d, J = 9.0 Hz, 3H), 7.32 (ud, J = 7.5, 1.4 Hz, 1H), 7.26 (s, 1H),
TA7 (t, J=7.1 Hz, 1H), 3.69 — 3.26 (m, LIT), 3.55 ~ 3.37 (m, LIT), 3.18 —- 2.98 (m, 211), 2.93 —- 2.80 (m, tH), 2.47 (d, J = 35.9 Hz, 1H), 1.31 — 1.12 (m, 9H); ESIMS m/= 580 (M+).
Example 18: Preparation of (Z)-3-(2,6-dimethylphenyl)-2-((¥)-(4-(1-(4- ] (trifluoromethoxy)phenyl)-14-1,2,4-triazol-3-yl)benzylidene)hydrazono)-1,3-thiazepane (Compound 211C) (Synthesis Method J) /=N
L0G
So z Non :
To (E)-N-(2,6-dimethylphenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)- L H-1,2 4- triazol-3-yl)benzylidene)hydrazinecarbothioamide (500 mg, (1.979 mmol) and potassium carbonate (541 mg, 3.92 mmol) in acetone (4 ml) was added 1-bromo-4-chlorobutane (0.135 ml, 1.18 mmol). The reaction was heated to 60 °C overnight. The alkylation was determined to be complete by ultra performance liquid chromatography (“UPLC”). The reaction mixture was diluted with DCM and washed with water. The aqueous layer was extracted with DCM.
The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided (17,N'F)-4-chlorobutyl N-(2,6-dimethylphenyl)-N'- : (4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2 4-triazol-3-yl)benzylidene)carbamo hydrazonothioate (427 mg, 0.710 mmol, 73%) as a yellow gum which was used without ; further purification. To (1ZN'E)-4-chlorobutyl N-(2,6-dimethylphenyl)-N'-(4-(1-(4- (trifluoromethoxy)phenyt)- 1 H- 1,2,4-triazol-3-yl)benzylidenc)-carbamohydrazonothioate (427 mg, 0.710 mmol), potassium iodide (236 mg, 1.42 mmol) and potassium carbonate (393 mg, 2.84 mmol) was added acetone (7 ml). The reaction was heated to 65°C for 72 h. The reaction was cooled to room temperature, diluted with DCM and washed with water. The aqueous \
layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided a yellow oil. The yellow oil was recrystallized from MeOll, filtered, washed with MeOH and dried to provide the title compound as a yellow solid (100 mg, 0.177 mmol, 25%): mp 100 - 106 °C; 'H
NMR (400 Mllz, CDCl3) 8 8.55 (s, 1D), 8.15 (d, J = 8.4 Iz, 211), 8.10 (s, 111), 7.79 (dt, J = 10.4, 5.8 Hz, 4H), 7.38 (d, J = 8.3 Hz, 2H), 7.11 (s, 3H), 3.85 — 3.78 (m, 2H), 3.20 —- 3.12 (m, 21D), 2.30 (s, 611), 2.13 = 2.07 (m, 2H), 1.87 — 1.82 (m, 211); ESIMS m/; 566 (M+).
Example 19: Preparation of (7)-3-(2-isopropylphenyl)-2-((F)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2 4-triazol-3-yl)benzylidene)hydrazono)-1,3-thiazinan- 4-one (Compound 224C) (Synthesis Method L) /=N
CE
Fo z NN 0 j
To (E)-N-(2-isopropylphenyl)-2-(4-(1-(4-(triflucromethoxy)phenyl)-1H- 1,2 4-mazol- 3-yhbenzylidene)hydrazinecarbothioamide (500 mg, 0.953 mmol) in butanone (9.5 ml) was added acryloyl chloride (0.077 ml, 0.953 mmol). The reaction was stirred at ambient temperature for 10 min followed by 50 °C for 2 h. The reaction was cooled to 40) °C overnight. The reaction was determined to be complete by LOMS. The reaction mixture was diluted with DCM and washed with saturated sodium bicarbonate. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided a yellow oil. The oil was recrystallized with dicthyl cther/hexancs to provide the title compound as a light yellow solid (125 mg, 0.217 mmol, 23%): mp 118 °C (dec); 'H NMR (400 MHz, CDCl3) 8 8.57 (s,
UD, 8.21 (d, J =8.41lz 211), 8.16 (s, 111), 7.85 — 7.75 (m, 411), 7.46 — 7.36 (m, 411), 7.33 — 7.26 (m, 1H), 7.10 (d, J = 7.6 Hz, 1H), 3.26 — 3.14 (in, 4H), 2.81 (heptet, J = 6.9 Hz, 1H). 1.21 (t, J =7.2 Hz, 611); ESIMS m/z 580 (M+I1). ]
Example 20: Preparation of (7)-3-(2,6-difluorophenyl)-2-((F)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazono)-1,3- thiazetidine (Compound 245C) (Synthesis Method J) /=N
F “7 S
A 0A 0
To a mixture of (F)-N-(2,6-difluorophenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)- 1 H- 1,2 4-triazol-3-yhbenzylidene)hydrazinecarbothioamide (0.50 g, 0.96 mmol) and potassium carbonate (0.53 g, 3.9 mmol) in butanone (10 mL) in a 25 mL vial equipped with a magnetic stir bar was added diiodomethane (0.093 ml, 1.2 mmol). The reaction was heated to 55 °C and stirred for two days. The reaction mixture was diluted with DCM, washed with water, and the phases separated. The aqueous phase was extracted with DCM and the combined organic phases were dried by passing through a phase separator cartridge and then concentrated. Purification by [lash column chromatography provided a yellow oil which crystallized upon standing. The solid was slurried in dicthyl ether and hexanes and collected by vacuum [iltration. The solid was washed with hexanes and dried to provide the title compound (0.086 g, 0.16 mmol, 17%) as a light yellow solid: mp 144 — 146 °C; "II NMR (400 MHz, CDCl) 8 8.58 (s, LH), 8.34 (s, 1H). 8.20 (d, J = 8.3 Hz, 2H), 7.81 (d, J = 8.8 Hz, 411), 7.40 (d, J = 8.3 Hz, 2H), 7.31 = 7.23 (m, LH), 7.03 ~ 6.97 (m, 211), 5.05 (s, 211); ESIMS m/z 532 (M+H).
Compounds 240 — 244 and 246 — 261, shown in Table 3, were prepared according to the method described in Example 20 from the appropriately substituted intermediates disclosed in Table 1. Characterization data [or these compounds is reported in Table 4.
Example 21: Separation of rotationally stable atropisomers from racemic mixtures :
Separation of constituent isomers from racemic mixtures can be carried out utilizing i onc of the following chiral HP1.C methods.
Separation Method A: The column used for separation was a Chiral Technologies INC
Chiral Pak [A 5 pm, 4.6 X 250 mim column (Part number 80325). The method consists of a 1.0 mL/min {low rate from {} to 30 min with an isocratic hold at 25% B for the duration of the run. The A cluent is n-hexane, the B cluent is iso-propyl alcohol.
Separation Method B: The column used for separation was a Chiral Technologies INC
Chiral Pak 1B 5 um, 4.6 X 250 mm column (Part number 81325). The method consists of a 1.0 ml/min flow rate from 0 to 30 min with an isocratic hold at 15% B for the duration of the run. The A eluent is n-pentane, the B eluent is n-butyl alcohol.
Example 22: Preparation of (E)-N-(2-fluoro-6-isopropylphenyl)-2-(4-(1-(4- (trifluoromethoxy)phenyl)-14-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (Compound 1-40; Synthesis Method C)
I
0.4.0 0.40 NH, g F
F. : Br — F. - Jo — Or —_— ra —
Method Method Method H H Method
M M M C
FX /=N oN “OL F
N S
No A 7
HH
Step 1: Preparation of 1-fluoro-2-nitro-3-(prop-1-en-2-yl)benzene (I-37, Method
M). To a mixture of I-bromo-3-fluoro-2-nitrobenzene (0.953 g, 4.33 mmol) in a 100 ml. round-bottomed flask equipped with a magnetic stir bar and nitrogen inlet were added dioxane (17.3 ml), sodium carbonate (0.551 g, 5.20 mmol), water (4.33 ml.), and 4,4,5 5- : tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (0.977 mL, 5.20 mmol). To this mixture was added bis(triphenyl-phosphine)palladium(Il)chloride (0.243 g, 0.347 mmol). The flask was evacuated and purged with nitrogen (3 x) and then heated to 80 °C and stirred overnight.
The reaction was cooled to room temperature, filtered through Celite ®, and the pad was washed with ethyl acetate. The phases were separated and the organic phase was concentrated. Purification by flash column chromatography provided the title compound (0.590 ¢, 3.26 mmol, 75 % yield) as a light yellow oil: 'H NMR (400 MIlz, CDCl3) § 7.48 — 7.36 (m, 1H), 7.21 = 7.06 (m, 2H), 5.23 (p, J = 1.5 Hz, I), 5.05 (q, J = 1.1 Hz, LH), 2.09 (s, 3H); PC NMR (101 MHz, CDCl) 8 153.56 (d. Jer = 257.5 Ha). 139.62. 139.60, 138.83, 131.48 (d, Joy = 8.6112), 124.47 (d, Jor = 3.6 Hz), 117.60, 115.51 (d, Jor = 10.1 Hz), 23.18.
Step 2: Preparation of 2-fluoro-6-isopropylaniline (1-38, Method M). To a solution of 1-fluoro-2-nitro-3-(prop-1-en-2-yhbenzene (0.590 g, 3.26 mmol) in ethyl acetate (32.6 mL) in a 250 mL round-bottomed flask equipped with a magnetic stir bar and nitrogen inlet was added palladium on carbon (5% Pd / C, 0.693 g, 0.326 mmol). The reaction flask 10° was evacuated and purged with hydrogen (2 x) and then placed under 1 atmosphere (atm) of hydrogen and stirred at room temperature overnight. The reaction was filtered through
Celite® and the pad was washed with ethyl acetate. The filtrate was concentrated (o give the title compound (0.423 g, 2.76 mmol, 85 % yield) as clear and colorless oil: IR (neat) 3476 (m), 3392 (m), 2966 (m), 2872 (m), 1628 (s), 1474 (s), 1270 (im) em; "H NMR (400 MHz,
CDCl) 36.92 (dt, J=7.7,1.2 Hz, 1H), 6.86 (ddd, J = 10.8, 8.1, 1.4 Hz, 111), 6.69 (td, J = 8.0, 5.6 Hz, 1H), 3.71 (bs. 2H), 2.92 (hept, J = 6.8 Hz, 1H), 1.26 (d. J = 6.8 Hz, 6H); °C
NMR (101 MHz, CDCl3) 8 151.91 (d, J = 237.6 Hz), 135.10 (d, J = 2.3 Hz), 131.60 (d, J = 11.8 Hz), 120.52 (d, J=3.0 Hz), 117.99 (d, J=8.0 Hz), 112.28 (d, J = 19.6 Hz), 27.77 (d, J = : 2.9 Hz), 22.22. 20) Step 3: Preparation of N-(2-fluoro-6-isopropylphenyl)hydrazinecarbothioamide ; (I-39, Method M). To a 100 mL round-bottomed flask equipped with a stir bar and nitrogen inlet were added 2-fluoro-6-isopropylaniline (0.415 g, 2.71 mmol), dichloromethane (13.6 ml), water (6.78 mL), and sodium bicarbonate (0.683 g, 8.13 mumol). To this biphasic mixture was added thiophosgene (0.199 ml, 2.60 mmol) and the reaction was stirred vigorously for 2 hours. The suspension was filtered through a phase separator cartridge and the organic phase was concentrated in a 100 mL round-bottomed flask. The flask was equipped with a magnetic stir bar and nitrogen inlet and the residue was dissolved in ethanol : (6.78 mL). To the resulting solution was added hydrazine hydrate (0.131 mL, 2.71 mmol) ; and the reaction was stirred at room temperature for 2 days. The solution was concentrated and the resulting residue was suspended in a mixture of diethyl ether and hexanes and re- concentrated to give a solid. The solid was suspended in a minimal amount of diethyl ether and the mixture was diluted with hexanes. The majority of the diethyl ether was evaporated and the resulting solid was collected by vacuum filtration, washed with hexanes and then dried under house vacuum to provide the title compound (0.518 g, 2.28 mmol, 84 % yield) as 36 i a white solid: mp 122-124 °C: 'H NMR (400 Ml17, CDCI3) 3 8.56 (bs, 111). 7.52 (bs, III), 7.32 (ud, J = 8.1, 5.6 Iz, 1H), 7.17 = 7.12 (m, LID), 7.00 (ddd, J = 9.5, 8.2, 1.4 L1z, LID), 4.07 (bs, 2H), 3.15 (hept, J = 7.0 Hz, 1H), 1.24 (d, J = 6.9 Hz, 611); ESIMS m/z 229 (M+).
Step 4: Preparation of (E)-N-(2-fluoro-6-isopropylphenyl)-2-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (I-40, Method C). To a solution of 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2 4-triazol-3- i yhbenzaldehyde (0.760 g, 2.28 mmol) in methanol (22.8 ml.) in a 100 ml. round-bottomed flask equipped with a magnetic stir bar and reflux condenser was added N-(2-{Tuoro-6- isopropylphenyhhydrazinecarbothioamide (0.518 g, 2.28 mmol), and the reaction was heated to 65°C and stirred for 6 hours. The temperature was lowered to 50°C and the reaction was stirred overnight. The reaction was cooled to room temperature and the resulting solid was filtered, washed with methanol, and dried under vacuum (25 in Hg) at 55 °C 10 give the litle compound (0.907 g. 1.67 mmol, 73 % yield) as a white solid: mp 210-212 °C: 'H NMR (400
MHz, CDC13) § 9.54 (s, 1H), 8.60 (s, 1H), 8.56 (s, 1H), 8.30 - 8.22 (m, 2H), 7.92 (s, 1H), 7.86 7.76 (m, 4k), 7.44 — 7.38 (m, 2H), 7.35 (dd, J =8.1, 5.6 Hz, 1H), 7.18 (d, J = 7.9 Hz, 1H), 7.04 (ddd, J =9.4,82, 1.3 Hz, 1H), 3.22 (p, J=6.9 Hz, 1H), 1.29 (d, J = 6.9 Hz, 6H);
ESIMS nv/z 544 (IM+111*). [termediate compounds I-32 — 1-36 and 1-41 - 1-65, shown in Table 1, were prepared according to the methods outlined in Example 22, Steps 1-4. Characterization data for these intermediates is shown in Table 2.
Example 23: BIOASSAYS ON BEET ARMYWORM (“BAW”) AND CORN EARWORM (“CEW”)
BAW has few elleclive parasites, diseases, or predators Lo lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops. In various places, it is of :
ECONOMIC concern upon asparagus, colton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon, among other plants. C1:W is also known to be resistant (0 certain insecticides. Consequently, : because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests. :
Certain molecules disclosed in this document were tested against BAW and CEW using procedures described in the [ollowing examples. In the reporting of the results, the “BAW & CEW Rating Table™ was used (See Table Scction).
Bloassays oN BAW (Spodoptera exigua)
Bioassays on BAW were conducted using a 128-well dict tray assay. One to [ive second instar BAW larvae were placed in cach well (3 ml.) of the diet tray that had been previously filled with 1 mL of artificial diet lo which 50 ug/em? of the test compound (dissolved in 50 pL. of 90:10} acetone-water mixture) had been applied (to cach of cight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover and held at 25 °C, 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table 5: Biological Results” (See Table Section). BioassaYs ON CEW (Helicoverpa zea)
Bioassays on CEW were conducted using a 128-well diet tray assay. One to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been : previously filled with | mL of artificial dict to which 50 ug/em? of the test compound (dissolved in 50 pL. of 90:10 acelone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover and held at 25 °C, 14:10 light-dark for live to seven days. Percent mortality was recorded for the larvae in cach well; activity in the cight wells was then averaged. The results are indicated in the table entitled “Table 5: Biological Results” (See Table Section).
Example 24: BIOASSAYS ON GREEN PEACH APHID (“GPA”) (Myzus persicae).
GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts : as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweel potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roscs. i
GPA has developed resistance to many pesticides.
Certain molecules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, the “GPA
Rating Table” was uscd (See Table Section).
Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were uscd as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for cach treatment. Test compounds (2 mg) were dissolved in 2 ml. of acetone/methanol (1:1) solvent, [orming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5X with 0.025% Tween 20 in [LO to obtain the solution at 200 ppm test compound. A hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/methanol (1:1) solvent. Treated plants were held in a holding room for three days at approximately 25 °C and ambient relative humidity (RH) prior lo grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W.S. Abbott, “A Method of Computing the Effectiveness of an
Insecticide™ J. Econ. Entomol. 18 (1925), pp.265-267) as follows.
Corrected % Control = 100 * (X - Y) / X where
X = No. of live aphids on solvent check plants and
Y = No. of live aphids on treated plants
The results are indicated in the table entitled “Table 5: Biological Results” (Sce
Table Section). PESTICIDALLY ACCEPTABLE ACID ADDITION SALTS, SALT DERIVATIVES, :
SOLVATES, ESTER DERIVATIVES, POLYMORPHS, ISOTOPES AND
RADIONUCLIDES
Molecules of Formulas One, Two and Three may be formulated into pesticidally : acceptable acid addition salts. By way of a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and : hydroxycthanesulfonic acids. Additionally, by way of a non-limiting example, an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnesiun.
Molecules of Formulas One, Two and Three may be formulated into salt derivatives.
By way of a non-limiting example, a salt derivative can be prepared by contacting a [ree base with a sufficient amount of the desired acid to produce a salt. A free base may be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (NaOH), potassium carbonate, ammonia, and sodium hicarhonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more water-soluble by converting it (o its dimethylamine salt.
Molecules of Formulas One, Two and Three may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as "solvates.” However, it is particularly desirable to form stable hydrates with water as the solvent. ;
Molecules of Formulas One. Two and Three may be made into ester derivatives.
These ester derivatives can then be applied in the same manner as the invention disclosed in this document is applied.
Molecules of Formulas One, Two and Three may be made as various crystal polymorphs. Polymorphism is important in the development of agrochemicals since different ; crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.
Molecules of Formulas One, Two and Three may be made with different isotopes. Of particular importance are molecules having B61 (also known as deuterium) in place of TH.
Molecules of Formulas One, Two and Three may be made with different radionuclides. Of particular importance are molecules having ™*C.
STEREOISOMERS
Molecules of Formulas One, Two and Three may exist as one or more slereoisomers.
Thus, certain molecules can be produced as racemic mixtures. [t will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers.
Individual stereoisomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starti ng materials, or by conventional resolution procedures.
INSECTICIDES
Molecules of Formulas One, 't'wo and Three may also be used in combination (such as, in a compositional mixture, or a simultancous or sequential application) with onc or more of the following insecticides — 1,2-dichloropropane, abamectin, acephate, acetamiprid, accthion, acctoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosullan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasinc, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexalluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin, butacarb, ; butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carhon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole,
I5 chlorbicyclen, chlordane, chlordecone, chlordimefoim, chlordimeform hydrochloride, ; chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin I, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, cypropen, cyromazine, cythioate, DDT, decarbofuran, deltamethuin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton- : 0, demeton-O-methyl, demeton-S, demecton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, : dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC- sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, esdepalléthrine, eslenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, a1 fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, (ipronil, {lometoquin, {lonicamid, flubendiamide (additionally resolved isomers thereof), flucofuron, flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufenprox, flufiprole, (Tupyradifurone, fluvalinate, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, fufenozide, furathiocarb, furethrin, gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imidaclothiz, imiprothrin, indoxacarb, iodomethane, [PSP, isazofos, isobenzan, isocarbophos, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, lutenuron, lythidathion, malathion, malonoben, mazidox, ME-5343, MEB-5343, mecarbam, mecarphon, menazon, meperfluthrin, mephosfolan, mercurous chloride, mesullenfos, metaflumizone, methacrifos, methamidophos, methidathion, methiocarb, methocrotophos, methomyl, methoprene, methothrin, methoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, monocrotophos, monomchypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nilluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin, : phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichior, phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp'-DDT, prallethrin, precocene I, precocene IT, precocene III, primidophos, profenofos, profluralin, profluthrin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pymetrozine, pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrin [, pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, guinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide, : spinetoram, spinosad, spiromesifen, spirotetramat, sulcoluron, sulcofuron-sodium,
sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tasmanone, tau-fluvalinate, tazimearb, TDL, tebufenozide, tebulenpyrad, tebupirimf{os, teflubenzuron. tefluthrin, temephos, TEPP, terallcthrin, terbufos, tetrachlorocthane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, thera-cypermethrin, thiacloprid, thiamethoxan, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap- disodium, thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin, transtluthrin, transpermethrin, triarathene, triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumuron, trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, and zolaprofos (collectively these commonly named insecticides are delined as the “Insecticide Group™).
ACARICIDES
Molecules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following acaricides — acequinocyl, amidoflumet, arsenous oxide, azobenzene, azocyclotin, benomyl, benoxalos, benzoximate, benzyl benzoate, bifenazate, binapacryl, bromopropylate, chinomethionat, chlorbenside, chlorfenethol, chlorfenson, chlorfensulphide, chlorobenzilate, chloromebuform, chloromethiuron, chloropropylate, clofentezine, cyenopyrafen, cyflumetofen, cyhexatin, dichlofluanid, dicofol, dienochlor, diflovidazin, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinopenton, dinosulfon, dinoterbon, diphenyl sulfone, disulfiram, dofenapyn, etoxazole, fenazaquin, fenbutatin oxide, fenothiocarb, fenpyroximate, fenson, fentrifanil, fluacrypyrim, fluazuron, flubenzimine, (luenetil, flumethrin, fluorbenside, hexythiazox, mesulfen, MNAF, nikkomycins, proclonol, propargite, quintiofos, spirndiclofen, sulfiram, sulfur, tetradifon, tetranactin, tetrasul, and thioquinox (collectively these commonly named acaricides are defined as the “Acaricide
Group™).
NEMATICIDES
Molecules of Formulas One, Two and Three may also be used in combination (such as, ina compositional mixture, or a simultancous or sequential application) with one or more : of the following nematicides — 1,3-dichloropropene, benclothiaz, dazomet, dazomet-sodium, :
DBCP, DCIP, diamidafos, fluensulfone, fosthiazate, furfural, imicyalos, isamidofos, isazofos, metam, metam-ammonium, metam-potassium, metam-sodium, phosphocarb, and thionazin (collectively these commonly named nematicides are defined as the “Nematicide Group™) 43
Cl
FUNGICIDES
Molecules of Formulas One, Two and Three may also be used in combination (such as. in a compositional mixture, or a simultaneous or sequential application) with one or more of the following fungicides — (3-ethoxypropyl)mercury bromide, 2-methoxyethylmercury chloride, 2-phenylphenol, 8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, : acibenzolar, acibenzolar-S-methyl, acypetacs, acypetacs-copper, acypetacs-zine, aldimorph, allyl alcohol, ametoctradin, amisulbrom, ampropylfos, anilazine, aureofungin, azaconazole, azithiram, azoxystrobin, barium polysulfide, benalaxy!, benalaxyl-M, benodanil, benomyl, benquinox, bentaluron, benthiavalicarb, benthiavalicarb-isopropyl, benzalkonium chloride, benzamacril, benzarmacril-isobutyl, benzamorf, benzohydroxamic acid, bethoxazin, binapacryl, biphenyl, bitertanol, bithionol, bixafen, blasticidin-S, Bordeaux mixture, boscalid, bromuconazole, bupirimate, Burgundy mixture, buthiobate, butylamine, calcium polysultide, captalol, captan, carbamorph, carhbendazim, carboxin, carpropamid, carvone, Cheshunt mixture, chinomethionat, chlobenthiazone, chloraniformethan, chloranil, chlorfenazole, chlorodinitronaphthalene, chloroneb, chloropicrin, chlorothalonil, chlorquinox, chlozolinate, climbazole, clotrimazole, copper acetate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zine chromate, cresol, culraneb, cuprobam, cuprous oxide, cyazotamid, cyclafuramid, cycloheximide, cyflufenamid, cymoxanil, cypendazole, cyproconazole, cyprodinil, dazomet, dazomet-sodium, DBCP, debacarb, decafentin, dehydroacetic acid, dichlofluanid, dichlone, : dichlorophen, dichlozoline, diclobutrazol, diclocymet, diclomezine, diclomezine-sodium, dicloran, diethofencarb, diethyl! pyrocarbonate, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, dinocap- 4, dinocap-6, dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine, dipyrithione, disulfiram, ditalimfos, dithianon, DNOC, DNOC-ammonium, DNOC-potassium, DNOC- : sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin-sodium, dodine, drazoxolon, edifenphos, epoxiconazole, etaconazole, etem, ethaboxam, ethirimol, ethoxyquin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, cthylmercury chloride, ethylmercury phosphate, etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin, fentin chloride, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, i fluopicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole,
flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminiunt, fuberidazole, furalaxyl, lurametpyr, furcarbanil, furconazole, furconazole-cis, furfural, furmecyclox, furophanate, glyodin, griseofulvin, guazatine, halacrinate, hexachlorobenzene, hexachlorobutadiene, hexaconazole, hexylthiofos, hydrargaphen, hymexazol, imazalil, imazalil nitrate, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, iodomethane, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, isovaledione, kasugamycin, kresoxim-methyl, mancopper, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid, mepanipyrim, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium, metam-potassiuny, metam-sodium, metazoxolon, metconazole, methasulfocarb, methfuroxam, methy! bromide, methyl isothiocyanate, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, metiram, metominostrobin, metrafenone, metsulfovax, milneb, myclobutanil, myclozolin, N-(ethylmercury)-p-toluencsulphonanilide, nabam, ; mpatamycin, nitrostyrene, nitrothal-isopropyl, nuarimol, OCH, octhilinone, ofurace, orysastrobin, oxadixyl, oxine-copper, oxpoconazole, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, penthiopyrad, phenylmercuriurca, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phosdiphen, phthalide, picoxystrobin, piperalin, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, ; potassium azide, potassium polysullide, potassium thiocyanate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineh, proquinazid, prothiocarb, prothiocarb hydrochloride, prothioconazole, pyracarbolid, pyraclostrobin, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroguilon, pyroxychlor, pyroxylur, quinacctol, quinacetol sulfate, quinazamid, quinconazole, quinoxyfen, quintozene, : rabenzazole, salicylanilide, sedaxane, silthiofam, simeconazole, sodium azide, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysuifide, spiroxamine, streptomycin, sulfur, sultropen, TCMTB, tebuconazole, tebufloquin, tecloftalam, tecnazene, tecoram, tetraconazole, thiabendazole, thiadifluor, thicyofen, thifluzamide, thiochlorfenphim, ; thiomersal, thiophanate, thiophanate-methyl, thioquinox, thiram, tiadinil, tioxymid, tolclofos- methyl, tolylfluanid, tolylmercury acetate, triadime fon, triadimenol, triamiphos, triarimol, triazbutil, triazoxide, tributyltin oxide, trichlamide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, uniconazole, uniconazole-P, validamycin, valilenalate, 45 ;
E vinclozolin, zarilamid, zinc naphthenate, zineb, ziram, zoxamide (collectively these commonly named fungicides are defined as the “Fungicide Group™).
HERBICIDES :
Molecules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following herbicides — 2,3,6-TBA, 2,3,6-TBA-dimethylamnionium, 2,3,6-TBA- sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2.4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2.4,5-T-isoctyl, 2,4,5-T-isopropyl, 2.4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2.4,5-T- triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-cthylhexyl, 2.4-
D-3-butoxypropyl. 2,4-D-ammonium, 2,4-DB, 2.4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D- dicthylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammoniunt, 24-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-
D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D- octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D- tetradecylammonium, 2,4-D-tricthylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-
D-trolamine, 3,4-DA, 3,4-DB, 3,4-DP, 4-CPA, 4-CPB, 4-CPP, acetochlor, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrolein, alachlor, allidochlor, alloxydim, alloxydim-sodium, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminocyclopyrachlor-methyl, ami nocyclopyrachlor- potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2- : hydroxypropyl)ammonium, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, asulam-potassium, asulam-sodium, atraton, atrazine, azalenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, benazolin- dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benfluralin, benfuresate, bensulfuron, bensulfuron-methyl, bensulide, bentazone, bentazone-sodium, benzadox, benzadox-ammonium, benzfendizone, benzipram, benzobicyclon, benzofenap, : benzofluor, benzoylprop, benzoylprop-ethyl, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bilanafos-sodium, bispyribac, bispyribac-sodium, borax, bromacil, bromacil- lithium, bromacil-sodium, bromobonil, bromobutide, bromolenoxim, bromoxynil, ; bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidarole, buthiuron, .
butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole, carfentrazone, carfentrazone-cthyl, CDEA, CEPC, chlomethoxyfen, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-niethyl, chloramben-methylammoniuim, chloramben- sodium, chloranocryl, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbromuron, chlorbutam, chloreturon, chlorfenac, chlorfenac-sodium, chlorfenprop, chlorfenprop-methyl, chlorflurazole, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron- i ethyl, chlomitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil. chlorprocarb, : chlorpropham, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulluron, cisanilide, clethodim, cliodinale, clodinafop, clodinafop-propargyl, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, ] clopyralid-tris(2-hydroxypropyl)ammonium, cloransulam, cloransulam-methyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumnyluron, cyanamide, cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyhalofop-butyl, cyperquat, cyperquat chloride, cyprazine, cyprazole, cypromid, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, dazomet, dazomet-sodium, delachlor, desmediphain, desmetryn, di-allate, dicamba, dicamba-dimethylammonium, dicamba-diolamine, dicamba- j isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba- sodium, dicamba-trolamine, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop- ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P- dimethylanumonium, dichlorprop-potassium, dichlorprop-sodium, diclolop, diclofop-methyl, : diclosulam, dicthamquat, dicthamquat dichloride, dicthatyl, dicthatyl-cthyl, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, dilenzoquat metilsulfate, diflufenican, diflufenzopyr, diflufenzopyr-sodium, dimefuron, dimepipcrate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb- diolamine, dinoseb-sodium, dinoseb-trolamine, dinoterb, dinoterb acetate, diphacinone- sodium, diphenamid, dipropetryn, diquat, diquat dibromide, disul, disul-sodium, dithiopyr, diuron, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, DSMA, ]
EBEP, eglinazine, eglinazine-cthyl, endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, i ethametsulfuron-methyl, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxyfen-ethyl, \ a7 ethoxysulfuron, ctinofen, etnipromid, etobenzanid, EXD, fenasvlam, fenoprop, fenoprop-3- butoxypropyl, fenoprop-butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenoxaprop, fenoxaprop-cthyl, fenoxaprop-P, ; fenoxaprop-P-ethyl, lenoxasulfone, fenteracol, fenthiaprop, fenthiaprop-ethyl, fentrazamide, fenuron, fenuron TCA, ferrous sulfate, flamprop, flamprop-isopropyl, flamprop-M, flamprop- methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, florasulam, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazolate, flucarbazone, flucarbazone-sodiun, flucetosulfuron, fluchloralin. [lufenacet, (lulenican, flulenpyr, : flufenpyr-ethyl, flametsulam, flumezin, flumiclorac, ftumiclorac-pentyl, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupropanate-sodium, {lupyrsulfuron, flupyrsulfuron-methyl-sodium, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, flurtamone, fluthiacet, fluthiacet-methyl, fomesafen, fomesalen-sodium, foramsulfuron, fosamine, fosamine-ammonium, furyloxyfen,
I5 glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammoniumn, glulosinate-P- sodium, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate- : isopropylammoniun, glyphosate-monoammonium, glyphosate-potassium, glyphosate- sesquisodium, glyphosate-trimesium, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin- ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammoniun, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, iodosulfuron- methyl-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, : isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA-2- ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine,
MCPA-cthyl, MCP A-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA- olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB,
MCPB-ethyl, MCPB-methyl, MCPB-sodium, mecoprop, mecoprop-2-ethylhexyl, mecoprop- dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop- methyl, mecoprop-P, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop- i potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medinoterb, medinoterb acetate, mefenacet, mefluidide, mefluidide-diolamine, melluidide-potassiunm, mesoprazine, mesosulfuron, mesosulturon-methyl, mesotrione, metam, metam-ammoniumn, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosul{uron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, niethiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, metsuliuron-methyl, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, monuron TCA, morfamquat, morfamquat dichloride, MSMA, naproanilide, npapropamide, naptalam, naptalam-sodiom, neburon, nicosulfuron, nipyraclolen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxyfluorten, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, pertluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenyhmercury acetale, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-tricthylammonium, picloram-tris(2- hydroxypropyl)ammonium, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron, primisulfuron-methyl, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, proglinazine- ethyl, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propoxycarbazone-sodiuny, propyrisul{uron, propyzamide, prosulfalin, prosulfocarh, prosulfuron, proxan, proxan-sodium, prynachlor, pydanon, pyraclonil, pyraflulen, pyrallufen-ethyl, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazosulfuron-cthyl, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridatc, pyriltalid, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrithiobac, pyrithiobac-sodium, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, rhodethanil, rimsulfuron, saflufenacil, sebuthylazine, sechumeton, sethoxydim, siduron, simazine, i simeton, simetryn, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sullallate, sulfentrazone, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, TCA-ammonium, TCA-calcium, TCA-cethadyl, TCA- magnesium, TCA-sodium, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim,
terbacil, terbucarh, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazalluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thiobencarb, tiocarbazil, tioclorim, topramezone, tralkoxydim, tri-allate, triasulluron, triaziflam, tribenuron, tribenuron-methyl, tricamba, triclopyr, triclopyr-butotyl, triclopyr-cthyl, triclopyr-tricthylammonium, tridiphane, trictazine, trifloxysulfuron, trifloxysulfuron-sodium, trifturalin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosul{uron, vernolate, xylachlor, (collectively these commonly named herbicides are defined as the “Herbicide Group™).
BIOPESTICIDES
Molecules of Formulas One, Two and Three may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more ; biopesticides. The term “biopesticide™ is used for microbial biological pest control agenls thatare applied in a similar manner to chemical pesticides. Commonly these are bacterial, but there are also examples of fungal control agents, including Trichoderma spp. and
Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents have also been controlled with microbial agents. One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of
Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological insecticides include products based on: 1. entomopathogenic fungi (e.g. Metarhizium anisopliae), 2 entomopathogenic nematodes (e.g. Steinernema feltiae); and : 3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).
Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia.
Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolerant or resistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect resistant property to the genetically modified organism. In onc embodiment, the Molecules of Formula
One, Two or Three may be used with one or more biopesticides in the area of seed (treatments and soil amendments. The Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology-based control) products. Copping 1..G. (ed.) (2004). ) ;
The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British
Crop Production Council (BCPC), Farnham, Surrey UK.
OTHER ACTIVE COMPOUNDS
Molecules of Formulas One, Two and Three may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more of the following: 1. 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro| 4,5dec-3-en-2-one; 2. 3-(4’-chloro-2,4-dimethylf |, I’-biphenyl}-3-y1)-4-hydroxy-8-oxa- | -azaspiro[4,5 |dec- 1) 3-en-2-one; 3. 4-[|(6-chloro-3-pyridinylmethylJmethylamino -2(5 H)-furanone; 4, 4-[{(6-chloro-3-pyridinyDmethyl]eyclopropylamino]-2(5H)-furanone; 5. 3-chloro-N2-[(1S)- I-methyl-2-(methylsulfonyDethy!|-N1-[2-methyl-4-1,2,22- tetrafluoro-1-(trifluoromethyljethyljphenyl}-1,2-benzenedicarboxamide; 6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide; 7. 2-cyano-N-ethyl-3-methoxy-benzenesullonamide; 8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide; 9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide; 10. 2-cyano-6-fluoro-3-methoxy-N, N-dimethyl-benzenesulfonamide; 11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; ! 12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; 13. 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]- I -methyl- | H-pyrazole-4- carboxamide; 14. N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-,u,a-trifluoro-p-tolyl) hydrazone; 15. N-ethyl-2,2-dichloro- 1-methylcyclopropane-carboxamide-2-(2,6-dichloro-a, a, a- trifluoro-p-tolyl) hydrazone nicotine; 16. O-{(E-)-[2-(4-chloro-phenyl)-2-cyano- 1-(2-tritfluoromethylphenyl)-vinyl]} $-methyl thiocarbonate; : 17. (F)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1 -miethylacetamidine; ! 18. I-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[ | ,2- ajpyridin-5-ol; 19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl) [phenyl mesylate; and 20. N-Ethyl-2,2-dichloro- 1 -methyleyclopropanecarboxamide-2-(2,6-dichloro- alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.
Molecules of Formulas One, Two and Three may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more compounds in the following groups: algicides, antifeedants, avicides, bactericides, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, molluscicides, plant activators, plant growth regulators, rodenticides, and/or virucides (collectively these commonly named groups are defined as the “Al Group™). It should be noted that compounds falling within the AI Group, Insecticide
Group, Fungicide Group, Herbicide Group, Acaricide Group, or Nematicide Group might be in more than one group, because of multiple activities the compound has. For more information consult the “COMPENDIUM OF PESTICIDE COMMON NAMES” located at http://www.alanwood.net/pesticides/index.html. Also consult “THE PESTICIDE MANUAL” 14th Edition, edited by C D S Tomlin, copyright 2006 by British Crop Production Council, or its prior or more recent editions.
SYNERGISTIC MIXTURES AND SYNERGISTS
Molecules of Formulas One, Two and Three may be used with the compounds in the a
Insecticide Group to form synergistic mixtures where the mode of action of such compounds compared to the mode of action of the Molecules of Formula One and Two are the same, similar, or different. Examples of modes of action include, but are not limited to: : acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor;
GABA-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane distupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs). Additionally, Molecules of Formula One and Two may be used with compounds in the Fungicide Group, Acaricide Group, Herbicide Group, or
Nematicide Group to form synergistic mixtures. Furthermore, Molecules of Formulas One,
Two and Three may be used with other active compounds, such as the compounds under the heading “OTHER ACTIVE COMPOUNDS”, algicides, avicides, bactericides, molluscicides, rodenticides, virucides, herbicide safeners, adjuvants, and/or surfactants to form synergistic mixtures. Generally, weight ratios of the Molecules of Formulas One, Two and Three in a synergistic mixture with another compound are from about 10:1 to about 1:10, preferably from about 5:1 to about 1:5, and more preferably from about 3:1, and even more preferably about 1:1. Additionally, the following compounds are known as synergists and may be used with the molecules disclosed in Formula One: piperonyl butoxide, piprotal, s propy! isome, sesamex, sesamolin, sulfoxide, and tribufos (collectively these synergists are defined as the “Synergists Group™).
FORMULATIONS
A pesticide is rarcly suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in an appropriate form, permitting casc of application, handling, transportation, storage, and maximun pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, ; microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra low volume solutions. For further information on formulation types see “Catalogue of
Pesticide Formulation Types and International Coding System™ Technical Monograph n°2, i
Sth Edition by Croplife International (2002).
Is Pesticides are applied most often as aqueous suspensions or emulsions prepared [rom concentrated formulations of such pesticides. Such water-soluble, water-suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or waler dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous : suspensions. Wettable powders, which may be compacted to form water dispersible granules, 200 comprise an intimate mixture of the pesticide, a cartier, and surfactants. The concentration of the pesticide is usually from about 10% Lo about 90% by weight. The carrier is usually chosen from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates, npaphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.
Emulsifiable concentrates of pesticides comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of walter-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are chosen from conventional anionic and non-ionic surfactants.
Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at 4 concentration in the range from about 5% to about 50% by weight.
Suspensions are prepared by finely grinding the pesticide and vigorously mixing it into a carrier comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic or natural gums may also be added, to increase the density and viscosity of the aqueous carricr. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.
Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil. Granular compositions usually contain from about ().5% to about 10% by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate
L5 particle size, in the range of from about (.5 to about 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying : to obtain the desired granular particle size.
Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic j rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. :
They can be applied as a seed dressing or as a foliage application with a dust blower machine.
It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.
Pesticides can also be applied in the form of an aerosol composition. In such compositions the pesticide is dissolved or dispersed in a carrier, which is a pressure- generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.
Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests cat the bait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harhorages.
F'umigants are pesticides that have a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its concentration and the exposure time. They are
: characterized by a good capacity for diffusion and act by penetrating the pest’s respiratory system or being absorbed through the pests cuticle. Fumigants are applied to control stored product pests under gas proof sheets, in gas scaled rooms or buildings or in special chambers.
Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govern the speed with which the active ingredient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.
Oil solution concentrates are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better penetration of crevices, and better adhesion to greasy surfaces.
Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non- ionic hydrophilic surface-active agent and (3) at least one ionic surface-active agent, wherein the globules having a mean particle diameter of less than 800 nanometers. Further information on the embodiment is disclosed in U.S. patent publication 20070027034 published February 1, 2007, having Patent Application serial number 11/495,228. For case of use, this embodiment will be referred to as “OIWE™.
For further information consult “Insect Pest Management” 2nd Fdition by D. Dent, copyright CAB International (2000). Additionally, for more detailed information consult : “Handbook of Pest Control - The Behavior, Life Iistory, and Control of Iouschold Pests™ by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.
OTHER FORMULATION COMPONENTS
Generally, when the molecules disclosed in Formulas One, Two and Three are used in a formulation, such formulation can also contain other components. These components include, but are not limited (o, (this is a non-exhaustive and non-mutually exclusive list)
wetters, spreaders, stickers, penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.
A wetting agent is a substance that when added to a liquid increases the spreading or penetration power of the liquid by reducing the interfacial tension between the liquid and the surface on which it is spreading. Wetting agents are used [or two main {unctions in agrochemical formulations: during processing and manufacture to increase the rate of welting of powders tn walter 0 make concentrates for soluble liquids or suspension concentrates; and during mixing of a product with water in a spray tank to reduce the wetting time of wellable powders and to improve the penetration of water into water-dispersible granules. Examples of wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule formulations are: sodium lauryl sulfate: sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphatic alcohol ethoxylates.
A dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of dispersion of the particles and prevents them from reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manulacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to : adsorb strongly onto a particle surface ard provide a charged or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents arc sodium lignosulfonaltes. For suspension concentrates, very good adsorption and stabilization are : obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldehyde condensates. Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionics such as alkylarylethylene oxide condensates and EQ-PQ block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed as dispersing agents.
These have very long hydrophobic ‘backbones’ and a large number of ethylene oxide chains forming the ‘teeth’ of a “comb” surfactant. These high molecular weight polymers can give very good long-term stability to suspension concentrates because the hydrophobic backbones ] have many anchoring points onto the particle surfaces. lixamples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldehyde condensates; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EOQ-PO block copolymers; and graft copolymers.
An emulsifying agent is a substance which stabilizes a suspension ol droplets of one liquid phase in another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifier blends contain alkylphcnol or aliphatic alcohol with twelve or more ethylene oxide units and the oil- soluble calcium salt of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance (“HLB™) values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EQ-PO block copolymer surfactant.
A solubilizing agent is a surfactant which will form micelles in water at : concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobic part of the micelle. The types of surfactants usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate ethoxylales, and methyl oleate esters.
Surfactants are sometimes used, either alone or with other additives such as mineral or vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the pesticide on the target. The types ol surfactants used for bioenhancement depend generally on the nature and mode of action of the pesticide. However, they arc often non-ionics such as: : alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates. :
A carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive ; capacitics, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wetllable powders, granules and water- ] dispersible granules. ;
Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil- in-water emulsions, suspoemulsions, and ultra low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most conumon) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of vegetable E and seed oils.
Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent separation and settling of the dispersed particles or droplets.
Thickening, gelling, and anti-settling agents generally fall into two categories, namely waler- insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate, and allapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds 1} and seaweeds or are synthetic derivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum. :
Microorganisms can cause spoilage of formulated products. Therefore preservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are : not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p- hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).
The presence of surfactants often causes water-based formulations to foam during mixing operations in production and in application through a spray tank. In order to reduce the tendency to foam, anti-foam agents are often added either during the production stage or : before filling into bottles. Generally, there are two types of anti-foam agents, namely silicones and non-silicones. Silicones arc usually aqueous emulsions of dimethyl polysiloxane, while the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the anti-foam agent is to displace the surfactant from the air-water interface. “Green” agents (e.g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodegradable and generally derived from natural and/or sustainable sources, e.g. plant and animal sources.
Specific examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl polyglucosides. i
For further information, see “Chemistry and Technology of Agrochemical ]
Formulations™ edited by D.A. Knowles, copyright 1998 by Kluwer Academic Publishers. ]
Also see “Insecticides in Agriculture and Environment — Retrospects and Prospects” by A.S.
Perry, I. Yamamoto, L. [shaaya, and R. Perry, copyright 1998 by Springer-Verlag.
PESTS
In general, the Molecules of T'ormula Formulas One, Two and Three may be used to control pests e.g. beetles, earwigs, cockroaches, flies. aphids, scales, whitellies, leafhoppets, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests in the Phyla Nematoda and/or Arthropoda.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta. 5 In another embodiment, the Molecules of Formulas One, Two and Three may be used : to control pests of the Order Anoplura. A non-exhaustive list of particular genera includes, but is not limited to, Haematopinus spp.. Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, :
Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus,
Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests in the Order Coleoptera. A non-exhaustive list of particular genera includes, ; bul is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp.,
Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp.,
Ceutorhynchus spp., Chaetocrnema spp., Coluspis spp., Ctenicera spp., Curculio spp.,
Cyclocephala spp.. Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp.,
Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp..
Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp.,
Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis,
Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris,
Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata,
Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalars, !
Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi,
Cryprolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cyvlindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hamper,
Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenys suturalis,
Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus communis, Meligethes aeneus,
Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilus surinamensis, Oulemna melanopus, Oulema oryzae, Phyllophaga cuyabana, Popillia juponica, Prostephanus truncatus, Rhyzopertha dominica,, Sitona lineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum,
Tribolium castaneum, Tribolium confusum, Trogode rma variabile, and Zabrus tenebrioides. [n another embodiment, the Molecules of Formulas One, Two and Three may be vsed to control pests of the Order Dermaptera.
In another embodiment, the Molecules of Formulas One, ‘Two and Three may be used to control pests of the Order Blattaria. A non-exhaustive list of particular species includes, : butis not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica,
Periplaneta americana, Periplaneta australasiae, Periplaneta hrunnea, Periplaneta
Juliginosa, Pycnoscelus surinamensis, and Supella longipalpa.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera : spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dusineura spp. Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp.,
Phorbia spp.. Tabanus spp., and Tipula spp. A non-exhaustive list ol particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, ¢
Aanastrepha obliga, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens,
Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis,
Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila rosae, Rhagoletis ; cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys : calcitrans.
In another embodiment, the Molecules of l'ormulas One, Two and Three may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular genera includes, but is not limited lo, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp.,
Lepidosaphes spp.. Lagynotomus spp., Lyvgus spp., Macrosiphum spp., Nephotettix spp.
Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp.,
Pseudococcus spp. Rhopalosiphum spp. Saissetia spp.. Therioaphis spp., Toumeyella spp. Toxoptera spp.. Trictleurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is not limited to, Acrostermun hilare, Acyrthosiphon pisum,
Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiellc aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi,
Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagberius fasciatus, Dichelops furcatus, Diuraphis noxia,
Diuphorina citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda, :
Eriosoma lanigerum, Eurygaster maura, Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus.,
Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus,
Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mchanarva frimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus : persicae, Nephotertix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxera vitfoliae, Physokermes piceae,, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii,
Poecilocapsus lineatus, Psallus vaccinicola, Pseuducysta perseae, Pseudococcus brevipes,
Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae,
Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera,
Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriuna.
In another embodiment, the Molecules of Formulas One, Two and Three may be used | : to control pests of the Order Hymenoptera. A non-exhaustive list of particular genera 3 includes, but is not limited to, Acromyrmex spp., Auta spp., Camponotus spp., Diprion spp., ]
Formica spp., Monomorium spp.. Neodiprion spp., Pogononmiyrmex spp., Polistes spp.,
Solenopsis spp., Vespula spp., and Xylocopa spp. A non-exhaustive list of particular species f includes, but is not limited wo, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium ; minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile. !
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Isoptera. A non-exhaustive list of particular genera includes, but is not limited to, Coptoternes spp.. Cornitermes spp., Cryptotermes spp... Heterotermes
Spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp.,
Microcerotermes spp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zoorermopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi, Reticuliterines banyulensis, Reticulitermes grassei,
Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular genera ; includes, but is not limited Lo, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphunia :
Spp.. Diatraea spp., Earias spp., Ephestia spp., Epimecis spp. Feltia spp., Gortyna spp.,
IS Helicoverpa spp., Heliothis spp. Indarbela spp., Lithocolletis spp., Loxagrotis spp., :
Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp.,
Spodoptera spp., Synanthedon spp., and Yponomeuta spp. A non-exhaustive list of particular : species includes, but is not limited to, Achaea janata, Adoxophyes orana, Agrotis ipsilon, :
Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacampiodes defectaria,
Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, :
Buccularrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa,
Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella,
Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella,
Ecdytolopha aurantianum, Elasinopalpus lignosellus, Ephestia cautella, Ephestia elutella,
Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa : armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, [Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana,
Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Melisa plana, Mythimna unipuncta, Neoleucinodes eleganialis,
Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandeinis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana,
Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, Tincola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera ; coffeae, and Zeuzera pyrina. :
In another embodiment, the Molecules of Formulas One. Two and Three may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp.,
Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.
In another embodiment, the Molecules of I'ormulas One, Two and Three may be used to control pests of the Order Orthoptera. A non-exhaustive list of particular genera includes, but is not limited to, Melanoplus spp., and Prerophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana,
Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria,
Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species : includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis, and Pulex irritans. :
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and :
Thrips spp. A non-exhaustive list of particular sp. includes, but is not limited to, IFrankliniella
Jusca, Frankliniella occidentalis, Frankliniellu schulizei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and
Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis,
Thrips tabaci.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Thysanura. A non-exhaustive list of particular genera includes, f i ; but is not limited to, Lepisma spp. and Thermobia spp.
In another embodiment, the Molecules of Formulas One, T'wo and ‘Three may be used to control pests of the Order Acarina. A non-exhaustive list of particular genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp. Epitrimerus spp.. Eriophyes spp., Ixodes spp.. Oligonychus spp.. Panonychus spp.,
Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, : but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, :
Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovutus,
Brevipalpus phoenicis, Dermacentor variabilis, Dermmatophagoides pteronyssinus,
Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus . citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus sanguineus, Sarcoptes scabiel, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.
In another embodiment, the Molecules of Formulas One, Two and Three may be used
I5 to conuol pest of the Order Symphyla. A non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata.
In another embodiment, the Molecules of Formulas One, 'T'wo and Three may be used to control pests of the Phylum Nematoda. A non-exhaustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp.,
Dirylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne
Spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. includes, but is not limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyne incognita,
Meloidogyne javanica, Onchocerca volvulus, Rudopholus similis, and Rotylenchulus reniformis.
For additional information consult “HANDBOOK OF PEST CONTROL — THE
BEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by Arnold Mallis, 9th
Edition, copyright 2004 by GIE Media Inc.
APPLICATIONS
Molecules of l'ormulas One, Two and Three are generally used in amounts {rom about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Amounts from ahout 0.1 grams per hectare to about 500 grams per hectare are generally preferred, and amounts from about | gram per hectare to about 50 grams per hectare are generally more preferred.
The area to which a molecule of Formulas One, Two and Three is applied can be any area inhabited (or maybe inhabited, or traversed by) a pest, for example: where crops, trees, : fruits, cereals, fodder species, vines, turf and omamental plants, are growing; where domesticated animals are residing; the interior or exterior surfaces of buildings (such as places where grains are stored), the materials of construction used in building (such as : impregnated wood), and the soil around buildings. Particular crop areas to use a molecule of
Formula One include arcas where apples, com, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use aluminum : sulfate with a molecule of I'ormula One when growing various plants.
Controlling pests generally means that pest populations, pest activity, or both, are reduced in an area. "This can come about when: pest populations are repulsed from an area; when pests are incapacitated tn or around an area; or pests are exterminated, in whole, or in : part, in or around an area. Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fi fty percent, preferably more than 90 percent. Generally, the area is nol in or on a human; consequently, the locus is generally a non-human arca. j
The Molecules of Formulas One, ‘I'wo and Three may be used in mixtures, applied simultancously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root system, to better withstand stressful growing conditions). Such other compounds are, for example, compounds that modulate plant ethylene receptors, most notably 1-methylcyclopropene (also known as 1-MCP).
The Molecules of Formulas One, Two and Three can be applied to the foliar and fruiting portions of plants Lo control pests. The molecules will either come in direct contact with the pest, or the pest will consume the pesticide when cating leaf, fruit mass, or extracting sap, that contains the pesticide. The Molecules of Formulas One, Two and Three can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a molecule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.
Generally, with baits, the baits are placed in the ground where, for example, termifes can come into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of a building, (horizontal, vertical, or slant surface) where, for example, ants, termites, cockroaches, and ies, can come into contact with, and/or be attracted to, the bait. E
Baits can comprise a molecule of Formula One, Two or Three.
The Molecules of Formulas One, Two and Three can be encapsulated inside. or placed on the surface of a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) (0 micrometer size (about 10-900 microns in diameter).
Because of the unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the Formula One, Two or Three may be desirable to control newly emerged larvae,
Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the Molecules of Formula :
One, Two or Three to a different portion of the plant. For example, control of foliar-feeding insects can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or hy treating the seeds of a plant before planting. i
Seed treatment can be applied to all types of seeds, including those from which plants genetically modified Lo express specialized traits will germinate. Representative examples : include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as “Roundup Ready” seed, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, drought resistance, or any other benelicial traits.
Furthermore, such seed treatments with the Molecules of Formula One, Two or Three may : further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields ‘at harvest time.
Generally, about 1 gram of the Molecules of Formula One, Two or Three to about 500 grams per 100,000 sceds is expected to provide good benefits, amounts from ahout 10 grams to about 100 grams per 100,000 seeds is expected (0 provide better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits. i [t should be readily apparent that the Molecules of Formulas One, Two and Three may be used on, in, or around plants genetically modified to express specialized traits, such : as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with “stacked” loreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, or any other beneficial traits. ]
The Molecules of Formulas One, Two and Three may be used for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping. The Molecules of Formulas One, Two and Three are applied, such as by oral administration in the form of. for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.
The Molecules of Formulas One, Two and Three may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese.
They may also be employed advantageously in pets such as, horses, dogs, and cats. Particular pests (o control would be [leas and ticks that are bothersome (0 such animals. Suitable formulations are administered orally to the animals with the drinking water or feed. The dosages and [ormulations that are suitable depend on the species, "The Molecules of Tormulas One, Two and Three may also be used for controlling : parasitic worms, especially of the intestine, in the animals listed above.
The Molecules of Formula One, Two, and Three may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.
Pests around the world have been migrating to new environments (for such pest) and therealler becoming a new invasive species in such new environment. The Molecules of
Formula One and Two may also be used on such new invasive species to control them in such new environment.
The Molecules of Formula One, Two, and Three may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting. pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants. The use of such molecules in such area is to benefit the plants being grown in the area.
Such benefits, may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingredients), : improving the vigor of a plant (e.g. improved plant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingredients), and improving the tolerance to abiotic and/or biotic stress of the plant.
Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy evaluation processes by various governmental authorities (local, regional, state, national, and international). Voluminous data requirements arc specified by regulatory authorities and must be addressed through data generation and submission by the product registrant or by a third party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These governmental authorities then review such data and if a determination of safety is concluded, provide the potential user or seller with product registration approval. Thereafter, in that locality where the product registration is granted and supported, such user or seller may use or sell such pesticide.
A molecule according to Formula One, Two, and Three can be tested to determine its efficacy against pests. Furthermore, mode of action studies can be conducted to determine if said molecule has a different mode of action than other pesticides. Therealter, such acquired data can be disseminated, such as by the internet, to third parties.
The headings in this document are for convenience only and must not be used to interpret any portion hereof.
TABLE SECTION
BAW & CEW Rating Table : % Control (or Mortality)
More than {) — Less than 50 bs
Not Tested
No activity noticed in this bioassay bp ‘GPA Rating Table % Control (or Mortality) :
More than 0 - Less than 80 CB
No activity noticed in this bioassay : 5
Table 1: Structures for Compounds
Fl
S
~yMr cl
FF HN :
FY Ne os ‘ \=N
H
N.S
N
I-5 N "2
F Ne os \=N
H
~. NS
NY
FF [IN
FY Ne 0 nT od
O—
IO
- FY S . ¢ 7 F | @ N NH
NN N-NH
F_0O ci
I-8 rr 3
F N NH
NY N-NH :
SY
0 \ rh 0
Fs <3 0
N-N NaN
Wo H rE O~
S : b
I-10 . 3 N-NH ;
: ; 3 } oF
F O
Sy ny
I-11 F N NH
N- nd \
F Oo
F j “orf ; 2 1-12 F TL \ re
FO S
Pr N
I-13 F N N-NH H \<\
F
/ syn (Cho 1-14 -NH
FO N
A N
E'} N \=N : soni) -15 -NH 1-15 pO N > N
F F N
\=N
H ;
S
Nop
I-16 EF HN on
H
S
NY
- FF HN 1-17 FY NS o—{ nT ;
H
S
~My 8 F HN
F Ne oN SK 1
S jes “i 1.19 HN
E Nx ;
On JK
Fy =N
H 5
S
NT
FE HN
1-20 rx Ne o—-{ nT [ 0 E
S
FF HN
1-21 FX Ne
OS
H
S
NT
FF HN
1-22 FX Ne 0 IJ a : ~ S
FF NY
123 XN “1 oO C i
S £ 1-24 : | HN
FX Ns
OTT
H
S
~N Nop
FF HN
1-25 eX Ne )@
ORT,
FN
.
S
NS
I-26 FF HN “oO \=N Br y
S
> F F \=N 3
H
S
~N Nop 1-28 EF HN "od nS bg oN “0
H
S
1-29 FF N WX {o> 0 N ~N \=N : 7
S y 1-30 F F HNN
Hod Ys TJ =N :
H
SN S
NY ;
I-31 FF HN.___N od ns J
S
I-32 HN. A
H H ;
S
Y-NH
AN N-NH 4 [-33 N-N 9
Fo
Fg ~N
Fg
F
/=N 0
I-35 r Jo o - /~N
S
F
136 70 Ney A i
H
Oc O° 1-37 Ore
NH, 1-38 F or
SF
1-39 EN
H H
FT —
FX LN .
O NZ F
140 “OL i
Noy N :
H H
: . 4
Oc 0
I-41 fon
F
NH,
F
F :
I-43 ¥ : aN A
HoT
FF
/~=N I
FX N ; 0 NZ S 1-44 i
NNN
HoH 0:10” ™ i
I-45 oO
F
Nil,
I-46 Go
F :
S F
1-47 HN. A
HoH
FF
/~=N
FX N F ;
Noy Ay
H H
0. 0 1-49 or
F
NH, 1-50 oe
F i
ANN F
H H
FF /~N
FX N
I-52 i
NNN F
HH
/~N F
LN =
N S
1-53 F w L "NTN
H H
FTF /~N E
FL) ~ 1-54 F N i
Ny SN
H H
F b o /<N
I-55 NG” r F
Fr
F F i /~N 1-56 vA F N
FF 0 :
H
F o& /~N F
NJ
157 eA F N \ i
FF ZN” °N
H H
: F
NE /=N
I-58 F OL
F F
FF
. TF
F F
/~N
F NJ
1-59 Fe OF N o
FF
H
- T
NE /~<N F
I NJ re r N S
FF Nog Ay
H H
: /~N
N
F
/~N
N
1-62 F 0
H
: /~N F 1-63 F N ]
NA
HH
FF
- /=N F :
HAO | i
I-64 F7} N i
NNN :
~N
F No) A
PR N $ - 9 ‘
No Ay
H H
Table 2: Analytical Data for Compounds in Table I. 1 13 199 ai m It, °C, or "I' NMR nD Synthesis MS p
Method °C) ( 8) i 5s (DMSO-d) 12.06 (s, LID), 10.19 (s, LID),
A Mel) 209-2101 | 9.42 (s, LEH), 8.22 (s, LH), 8.17-8.03 (m,
SH), 7.66-7.57 (m. 4H), 7.42-7.38 (m, 2H) (CDCl3) 9.30 (5, 111), 8.69 (s, 111), 8.60 (s, i 9 _ 1 A .
Ls c 511 2022s | LHD. 8.26 (d. J =8.4 Hz, 2H), 7.89 (s, LHD,
M+1) 7.81 (m, 4H), 7.41 (d, J = 8.4 Hz, 2H), 7.19 (m, 31D), 2.35 (s, 61D) (CDCl) 8.90 (s, LH), 8.80 (s, LH), 8.6 (s, c 555 | 306009 | 1FD- 8:28 (d, J = 8.4 Hz, 2H), 8.9-8.7 (m, (M+1D) 410), 7.4 (d, J = 8.6 Hz, 2H), 6.7 (s, 2H), 3.80 (s, 3H), 2.39 (s, 311), 2.32 (s, 611) (CDCl3) 9.88 (s, 1H), 8.61 (s, 1H), 8.60 (s, 7 c 541 apoio | THD, 8.27 (d, J = 8.4 11z, 2H), 7.9 (s, 11D), (M+H) 7.9.7.7 (m, 4H), 7.4 (d, J = 8.6 Hz. 2H), 6.7 (s, 2H), 3.81 (s, 3H), 2.33 (s, 6H) (CDCl) 10.2 (s, LIT), 8.7 (s, LIT), 8.6 (s, 1H), 8.25 (d. J = 8.4 Hz, 2H), 8.0 (s, 1H),
QOS5_10¢C 3
BL 195-199 5 oo on aH). 7.4 (d, J = 8.4 Hy, 2H), 7.0 (s, 21D), 3.82 (s, 311) (CDCls) 9.89 (s, LH), 8.60 (s, 21), 8.25 (d, 591 J =8.5 Hz, 2H), 7.95 (s, 1H), 7.88-7.70 : - 233-27 19 C Men) | 233-236 (m, 411), 7.41 (d, J = 9.0 I1z, 2H), 6.70 (s, 2H), 3.81 (s, 3H), 2.31 (s, 6H) ] (CDCl3) 9.93 (s, 1H), 8.69 (s, 1H), 8.60 (s, . 525 LH), 8.26 (d, J = 8.4 Hz, 211), 7.93 (d, J = :
I-1 23()-2 Gs 0 ¢ Mt) | 07240 9 5 1, 20, 7.95 (s, 1H). 7.86-7.75 (mm, 411), 6.69 (s, 2H), 3.81 (s, 3H), 2.31 (s, 611)
v .
Synthesis mp IL, *C, or "F NMR
ID yninesk: MS
Method °C) (S) (CDCLy) 9.62 (s, 1H), 8.70 (s, LH), 8.60 (s, . 561 ane | TTD), 8.26 (d, J = 8.4 11z, 211), 7.92 (s, 11D), 214.0
I-11 ¢ M+) | B38 7.86-7.75 (im, 4ED), 7.41 (d, J = 9.0 Hz, 2H), 7.18 (m, 3H), 2.35 (s, 6H) (CDCl) 10.2 5, 11), 8.90 (s, 111), 8.62 (s, . 577 en | THD, 8.25 (d, J = 8.4 Haz, 211), 7.98 (s, 111),
I-12 C os | P7090 5.977 (4k), 7.4 (m, 3H), 6.8 (m. 2H), 3.82 (s, 311), 2.37 (s, 311) (CDCl) 9.9 (s, 1H), 8.6 (s, 1H), 8.23 (d, J = 8.4 Hz, 281), 7.9 (s, 111), 7.8 (d. J =8.6 541 Hz, 211), 7.75 (d, J = 8.4 17, 211), 7.7 (d, J 113 B Mt) | BBO CT TE). 7.45-7.35 (mm, 41), 6.91 (d. J =8 Hz, 2H), 5.73 (m, 1H), 3.80 (s, 3H), 1.65 (d, J = 7.2 Liz, 311) (CDCl) 9.32 (5, LH), 8.6 (s, 1H), 8.22 (d, 559 J = 8.4 Hz, 2H), 7.85-7.7 (m, SH), 7.6 (d, J
I-14 B Naty | 196-203 | = 6 Ha, 1D), 7.4 (d, J =8.5 Hz, 21D), 7.25. 7.15 (m, 2H), 6.93 (m, 1H), 5.7 (m. LH), 3.89 (s, 3), 1.67 (d, J = 6 Hz, 3H) (CDCI) 9.32 (s, LI), 8.61 (s, 111), 8.27 (d, = 7.2 - -
SUL | gion | / = 8:4 Hz, 2H), 7.97.7 (mm, 6H), 7.57.3 (M+H) (m, THY, 5.76 (m, 1H), 1.67 (d, J = 7 Hz, 311) (CDCl3) 9.37 (s, TH), 8.63 (s, LH), 8.60 (s,
A 9) 4 _ [ o> .
Lie c 525 218.205 | 1D, 8.26 (d. J =8.4 Hz, 2H), 7.89 (5, 111), (M+1) 7.85-7.76 (m, 4k), 7.41 (d, J = 8.4 Hz, 2H), 6.97 (s, 2H), 2.32 (s, 3H), 2.30 (s, 6H) (CDCl) 10.2 (s, LH), 9.07 (s, LI), 8.63 (5, 525 LHD), 8.25 (d, J = 8.4 Hz, 211), 8.0 (s, LH),
I-17 C (Varn | 168-180 | 7.9-7.7 (m, 4H), 7.65 (d. J = 8 Hz, 1H),
MH) 7.4-7.25 (m, 5H), 3.25 (heptet, J = 7 Hz,
LID, 1.35 (d, J = 7 tz, 6F1) (CDCL3) 89.29 (s, 1H), 8.87 (s, 1H), 8.59 (s, 11), 8.31 8.19 (m, 211), 7.90 — 7.84 539 (m, 2H), 7.85 — 7.79 (m, 2H), 7.73 (dd, J =
C (M41) 216-221 | 7.5, 1.7 Hz, 1H), 7.39 (dd, J = 12.6, 5.1
Fz, 310), 7.35 — 7.27 (m, 211), 3.37 = 3.04 (m, 11D), 2.40 (s, 3H), 1.29 (d, J = 7.5 lz, : 6H)
Method °C) (S (CDCl) 8 9.74 (s, LH), 9.06 (s, 1H), 8.69 500 (s, 111), 8.31 — 8.20 (m, 211), 7.98 — 7.84
C M1) | 223-223 | (mm, 311), 7.80 (m, 4H), 7.65 (d, J = 1.4 Hz, 1H), 7.43 — 7.28 (m, 3H), 3.19 (heptet, J = 6.9 Hz, 111), 1.32(d, J = 6.9 117, 611) (CDCl) 89.52 (5, HHL), 9.31 (s, 1H), 8.66 (d, J =8.2 Hz, LH), 8.60 (s, LH), 8.25 (d, J = 8.4 Hz, 211), 7.87 (5, IH), 7.86 ~ 7.80 1.20 c 538 220 | (m, 200), 7.77 (d, J = 8.4 Hz, 21D), 7.41 (d, ” (M+H) | (deo) | J=8.3 Hz 2H), 7.32 (ddd, J = 13.9,2.7.2, 4.3 Hz, 1H), 7.24 = 7.15 (m, 21), 6.27 (5, 111), 2.03 (d, J = 1.3 Hz, 3H), 1.73 (d, J = 1.1 Hz, 3H) (CDC) § 9.48 (s, 1), 9.14 (s, 111), 8.60 (s, LHD. 8.26 (d, J = 8.4 Hz, 2H), 7.92 (s.
S40 207- | 1H), 7.87 (d. J =7.7 Hz, 1H), 7.84 ~ 7.76 1-21 C ein | 210: | (m, 41D, 7.40 (d, J =8.3 117, 21D), 7.30 (dx, 215-218 | J =8.2,3.7 Hz, 1H), 7.28 - 7.23 (m. 2H), 2.57 (d, J=7.2 Hz, 2H), 1.93 (dg, J = 13.6, 6.7 Hz, 111), 0.98 (d, J = 6.6 Hz, 6H) (CDCl3) 8 9.46 (s, LH), 9.05 (s. 1H), 8.60 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.91 (s, 540 1H), 7.84 — 7.74 (m, 4H), 7.69 (d, J = 7.4 1-22 C (stp | 210-215 | Hz, 1H), 7.40 (d. J = 8.3 Hz, 2H), 7.36 - 7.27 (m, 3H), 2.91 (dt, J = 13.9, 6.9 Hz,
LH), 1.75 — 1.58 (m, 2H), 1.30 (d, J = 6.9
Hz, 3H), 0.92 (1, J = 7.4 Hz, 3H). (CDCl3) 8 9.41 (s, 1H), 9.01 (s, 117), 8.74
S60 (d, J =7.7 lz, 111), 8.60 (s, LI), 8.15 (d, J 1-23 C MatD | 213-216 | =8.4 Hz, 2H), 7.86 ~ 7.78 (m, 2H), 7.69 (s, LH), 7.57 - 7.44 (m, 611), 7.42 (d, J = 9.1 Hz, 2H), 7.37 = 7.27 (m, 411). (CDCl3) $9.65 (d, J = 17.9 Hz. 1H), 9.20 (s, 111), 8.60 (s, 1H), 8.27 (dd, J = 8.0, 4.5 $24 200- | Hz, 31D), 7.89 (s, 111), 7.86 - 7.75 (m, 411), 1-24 C Mary | 206 | 741d, /=8.3 He, 2H), 7.30 -7.27 (m, 210-211 | 11), 7.18 (q, J = 7.8 Hz, 2H), 2.00 - 1.90 (m, 111), 1.09 — LOL (m, 2H), 0.81 - 0.73 {m, 2H). :
1 13 {9 cia m TH, “C,or "F NMR
ID Synthesis MS ’ P
Method °C) to) (DMSO-d) 8 12.13 (s, TH), 10.07 (s, LH). 550 0.44 (s. 111), 8.23 (5. 111), 8.16 (d, J = 8.4 1-25 C (at | 221-223 | Hz 2HD, 8.13 ~ 8.06 (m. 2H), 801 - 7.98 (m, 3H), 7.63 (d, J = 8.4 Hz, 2H), 7.38 — 7.26 (m, 311), 7.23 (¢, Jyp= 74.1 Hz, 110) (CDCly) 89.37 (s, LH), 8.60 (s, LH), 8.57 500 |, (s. 1H), 8.27 (d, J = 8.4 Hz, 2H), 7.90 (s. - 10.7
I-26 C ath | 22023010. 7.81 tJ =8.5, 4.8 117, 411), 7.41 (d,
J=8.3 Hz, 2H). 7.31 (s. 2H). 2.31 (s, 60) (CDCl3) $9.39 (s, LT), 9.15 (s, LH), 8.61 (s. 111}, 8.29 (d, J = 8.4 Hz, 211), 8.16 — 556 8.05 (my, 2H). 7.95 = 7.85 (m, 3H), 7.85 - ~ 190 - 1-27 C etn) | 919219 96 (mm, 41), 7.41 (d, J = 8.3 Hz, 2H), 4.39 (q, J = 7.1 Lz, 2H), LAL (tJ = 7.1
Hz, 3H) (300 MHz, CDC13) 8 10.17 Gs, 1H), 9.09 (s, 1H), 9.03 (t, J = 5.4 Hz, LH), 8.60 (5, LH), 52g 8.23 (1, J = 8.9 Hz, 2H), 7.89 — 7.76 (m. 1-28 C oatn | 219-221 | 5H.7.39 (4, 1 =7.2 He, 2H), 7.17 - 7.07 (m, 11), 7.03 (d, J = 7.8 Hz, LH), 6.94 (d,
J=69 Hz, LH), 4.18 (q, J = 7.1 Hz, 2H), 1.61 (t, J = 7.0 Hz, 31) (DMSO-dq) 89.44 (s, 1H), 8.49 (s, LH), 8.42 (d, J=572 Hz, 1H), 8.29 8.21 (m, 499 21), 8.16 (d, J =8.5 Hz, 2H), 8.10 (d, J = 2D O08." 129 C Mel) | 127200 3 1, 8.08 (d. J = 3.0 Hz, LH), 8.04 (tJ = 6.5 Hz, 2H), 7.63 (d, J = 8.3 Hz, 3H), 2.29 (s, 310). (CDCls) 6 8.60 (s, LH), 8.31 (5, 1H), 8.24 (d, J = 8.4 Hz, 2H), 8.16 (d, J = 3.9 Hz, 499 | 11), 7.95 (d, J = 8.4 Hy, 211), 7.82 (d, J = : 1-30 ¢ Man) | THB 9 01, 21), 7.55 (J = 6.7 Hz, LHD. 7.41 (s, 2H), 6.99 (dd, J = 7.4, 5.1 Hz, 1H), 2.35 (s, 310). (CDCl3) § 8.60 (s. 111), 8.32 (s, LH), 8.25 : (d, J=8.4 Hz, 2H). 8.19 — 8.16 (m, 1H), : 131 o 513 | (0 19s | 7:97 (d, /=8.4 117, 21), 7.84 ~ 7 81 (m, (M+1) 2H), 7.58 (d, J =7.5 Hz, 1H), 7.40 (d. J = 8.3 Hz, 2H), 7.03 (dd. J = 7.5, 5.1 Hz, 1H). 2.67 (s. 210), 1.35 (t, J = 7.5 Hz, 310).
1 13 19 cia m II, ’C,or 'F NMR nD Synthesis MS P
Method Cy (8! 210 (CDC13) 8 8.97 (bs, 1H), 7.74 — 7.11 (m, 1-32 M . 511), 4.06 (bs, 2H), 3.11 (hept, J = 6.9 117, (IMT) 1H), 1.24 (d. J = 6.9 Hz. 6H) (DMSO-ds) & 11.87 (s, LH), 10.08 (s, 1H), 9.44 (s, 111), 8.20 (s, 111), 8.17 — 8.02 (m, 611), 7.63 (d, J = 9.0 Hz, 211), 7.39 — 7.35 (m, 1H), 7.35 — 7.28 (m, 1H), 7.27 = 7.18 575 (m, 211), 3.19 = 3.05 (m, 11D), 1.20 (d, J = 1-33 Co vey | 214210 16.9 Ha, 1; 197: NMR (376 MI1z, DMSO-de) 8 -85.20, -86.94 (CDCl3) 8 8.50 (s, LH), 8.07 (d, J = 8.1 Hz, 2H), 7.56 (d, J =2.1 Hz, 1H), 7.44 (dd, J = 317 8.6.2.2 Hz, 11D), 7.29 (d, J = 8.0 Hz, 211), 1-34 p* . 7.19 (d, J = 8.6 Hz, 1H), 2.42 (s, 3H); (IM+HTH
NMR (376 Mliz, CDCl3) & -49.69 (CDCly) § 10.09 (s, 111), 8.55 (m, 1H), 8.37 (m, 1H), 8.22 (m, 1H), 8.00 (m, 1H), ; 330) 7.57 (dd. J =5.3,2.2 Hz, LID, 7.51 (m, 1-35 P* . IH), 7.46 (m, 1H), 7.21 (m, {11}; (IMAL)
F NMR (376 Ml1z, CDCl;) § -49.61 (CDCl) 39.47 (s, LIT), 9.05 (s, 111), 8.54 (s, LH), 8.25 (d, J = 8.4 Hz, 2H), 7.92 (s, 1H), 7.78 (d, J = 8.4 117, 211), 7.71 —- 7.62 (m, 11), 7.57 (t, J = 2.7 Hz, 111), 7.46 (dd, 136 c 521 200 | J=8.6,2.2 Hz 1H), 7.41 — 7.29 (mn. 3H), : (IM+HT") | (dec) |7.21(d, J=8.6 Fz, 111), 3.19 (dt, J = 13.8, 6.9 Hz, 11), 1.32 (d, J = 6.9 Hz, 6H); 19F NMR (376 MHz, CDCl3) § -49.62
1 13 19 3 nei m IH, ’C,or 'FNMR
ID Synthesis MS P
Method °C) (8 (CDCl) 8 7.48 — 7.36 (m, 1H), 7.21 — 7.06 (m. 211), 5.23 (p. J = 1.5 Hz, 111), 5.05 (q,
J = 1.1 Hz, LH), 2.09 (s, 3H); 1-37 M BC NMR (101 Miz, CDCL) 8 153.56 (d,
Jer =257.5 112), 139.62, 139.60, 138.83, 131.48 (d, Jor = 8.6 HZ), 124.47 (d, Jeg = 3.6117), 117.60, 115.51 (d, Jeg = 19.1 Hz), 23.18 (CDC) § 6.92 (dt, J =7.7, 1.2 Hz, 1H), 6.86 (ddd, J = 10.8, 8.1, 1.4 Hz, 111), 6.69 (td, J = 8.0, 5.6 Hz, 1H), 3.71 (bs, 2H), 2.92 (hept, J = 6.8 Hz, 1H), 1.26 (4, J= 6.8 tiz, 6H): 1-38 M
HC NMR (101 MHz, CDCl3) § 151.91 (d,
J =1237.6 Hz), 135.10 (d, J = 2.3 H2), 131.60 (d, J = 11.8 Hz), 120.52 (d, J =3.0
Hz), 117.99 (d, /=8.0Hz2), 112.28. J = 19.6 Hz), 27.77 (d, J = 2.9 Hz), 22.22 (CDCly) 8 8.56 (bs, 111), 7.54 (bs, 111), 7.32(td, J = 8.1, 5.6 Hz, 1H), 7.17 = 7.09 229 (m, 1H), 7.00 (ddd, J =9.5, 8.2, 1.4 Hz, - I _1N4 1-39 M (mst | 22 124111), 4.07 (bs, 21D), 3.15 (hept, J = 7.0 Hz, : 1H), 1.24 (d, J = 6.9 Hz, 6H), 7.78 = 7.39 (m, 1H) (CDCl) 89.54 (s, 1H), 8.60 (s, 111), 8.56 (s, 1H), 8.30 — 8.22 (in, 2H), 7.92 (s, LH), sda 7.86 — 7.76 (m, 411), 7.44 — 7.38 (m, 21D),
C (MF | 210-212 | 7.35 (dd, [= 8.1, 5.6 Hz, 11D), 7.18 (d, J = 7.9 Hz, TH), 7.04 (ddd, J = 9.4, 8.2, 1.3 lz, 111), 3.22 (p, J = 6.9 Iz, 11), 1.29 (d,
J = 6.9 Hz, 611):
Synthesis mp "1, °C, or "FNMR
ID MS
Method °CH (5 (CDCl) 8 7.60 (dd, J =8.2, 2.5 Hz, 1H), 7.37 -7.21 (m, 211), 5.19 (p, J = 1.5 117, 1H), 4.97 — 4.89 (m, 1H), 2.11 — 2.04 (m, 3H): 1-41 M
BC NMR (101 Mllz, CDCl) 8 160.96 (d,
J =250.8 Hz), 148.46, 141.88, 135.18 (d, J =4.1 Hz), 132.09 (d, J=7.8 [17), 119.98 (d, J =20.9 liz), 115.99, 111.63 (d, J = 26.4 Hz), 23.35 (CDCl) 8 7.05 (dd, J =8.5, 6.4 Hz, 11D), 6.45 (1d, J = 8.5, 2.6 Hz, 1I1), 6.37 (dd, J = 10.6, 2.6 Hz, 1H). 3.74 (bs, 2H), 2.83 (hept, J =6.8 Hz, 1H), 1.24 (d, J = 6.8 Hz, 6H);
I-42 M
IC NMR (101 MHz, CDCl3) 8 161.75 (d,
J =2413 Hz), 144.76 (d, J = 10.3 Hz), 128.11 (d, J = 2.8 Hz), 126.53 (d, J = 9.6
Hz), 105.06 (d, J = 20.7 Hz), 102.26 (d, J =24.2 Iz), 27.27, 22.35 . (CDCl) 89.11 (bs. 1H), 7.44 (bs, 2H), al — ol wi 3 : 143 M | | 133135 135 72 (m, 1H), 699 (s, LH), 403 os, (IM-HTY 2H), 3.05 ¢hept, J = 6.9 Hz, 1H), 1.23 (d, J = 6.9 Hz, 6H) (CDCl) § 9.45 (s, 1H), 9.13 (s, 111), 8.60 ; (s, LI), 8.32 8.21 (m, 21D), 7.92 (s, 1H), -” 7.87 —7.75 (m, 4H), 7.64 (dd, J = 9.9, 2.7
C AM] I 217-222 | Hz, 110), 7.46 — 7.37 (m, 2H), 7.32 (dd, J = 8.8, 6.2 Hz, 1H), 7.02 (td, J = 8.3, 2.8 Hz, 1H), 3.14 (hept, J = 6.9 Hz, LH), 1.31 d, J =6.9 Iz, 611) (CDCI) 37.96 (dd, J = 9.0, 5.1 Hz, LH), 7.08 (ddd, J = 9.0, 7.4, 2.8 Hz, 1H), 7.02
I-45 M (dd, J =8.7,2.8 Hz, 11),5.20(p, J = 1.5 :
Hz, LH), 4.96 (p. J = 1.0 Hz, 1H), 2.11 — : 2.06 (m, 3H)
-
In oe MS
Method (°C (5
CDCly) 6 6.85 (dd, J = 10.3, 2.9 Hz, LH). 6.72 (td, J = 8.3, 2.9 Iz, 11), 6.60 (dd, J = 8.6, 5.1 Hz, 1H), 3.49 (bs, 2H), 2.88 (hept,
J=68 1H), 1.24 (d, J = 6.8 Hz, 6H); 1-46 M --
BC NMR (101 Mllz, CDCl3) 8 156.92 (d,
Jer =235.0 Hz), 139.17 (d, Jer =2.1 Ha), 134.61 (d, Joep = 6.2117), 116.55 (d, Jor = 7.5 Hz), 112.69 (d, Jer =22.5 Hz), 112.17 d, Jer =22.4 Hz), 27.90, 22.11 : (CDCl) 8 8.88 (bs, 1H) 7.42 (bs, 111), 7.03 : L47 M 22 163.17 | (4d: J = 100.29 Hz, LH), 6.93 (dad, J = (IM+H]") 8.7,7.7, 3.0 Hz, 1H), 4.03 (bs, 2H), 3.14 - : 3.00 (m, 1H), 1.23 (d, J = 6.9 Hz, 61) (300 MHz, CDCl3) 8 9.55 (s, LH), 8.90 (s, 1H), 8.59 (s, 1H), 8.30 — 8.21 (m, 2H), sud 7.92 (s, 1H), 7.85 = 7.74 (m, 411), 7.54 (dd, :
C (MH) 219-221 | J=8.8,5.5 Hz, 1H), 7.40 (d. J = 8.6 Hz, : 2H), 7.07 (dd, J = 10.0, 2.9 Hz, 1H), 6.97 © td, J=8.2,2.9 Hz, 111), 3.24 - 3.08 (m, 1H), 1.29 (d, J = 6.9 Hz, 6H) (CDCL;) 87.64 (dt, J = 8.1, 1.2 Hz, 1H), 7.39 (td, J = 8.2, 5.4 Hz, LID), 7.31 (td, J = 8.5. 1.2 Hz, 1H), 5.28 (p. J = 1.5 Hz, 1H), 491 (p,J= 1.0 Hz, 1H), 2.16 (t, J=1.3 :
Hz, 3D; :
M
PC NMR (101 MHz, CDCl3) $ 159.59 (d,
J =2493 Hz), 149.81, 136.14, 128.57 (d, J : =9.0 Hz). 127.02 (d, J = 22.0 Hz), 119.84 : (d,J=234 Hz), 119.41 (d, J = 3.6 Hy), 117.25, 23.10 (d, J = 1.9 Hz)
1 13 19 wei m IT, "CC, or :F NMR
D Sythosis MS ’ P
Metho °C) (8)
CDCl) 8 6.92 (td, J=8.1, 6.1 Hz, 1H), 6.44 (ddd, J = 10.4, 8.1. 1.1 117, 211), 3.72 (bs, 2H), 3.06 (heptd, J = 7.1, 1.3 Hz, LH), 1.35 (dd, J =7.1, 1.5 Hz, 6H); i 1-50 M Be NMR (101 MIlz, CDCly) 8 162.83 (d,
J=243.4 Hz), 145.29 (d, J = 8.8 Hz), 127.08 (d, J= 11.2117), 119.64 (d. J = 16.1 Hz), 111.77 (d, J = 2.3 Hz), 106.47 (d, J =242 Hz), 25.65,2097 (d, J =3.8
Hz) q (CDCl) 8 8.91 (bs, LH), 7.42 (bs, 111), 22% 15 _7¢( ost 2 = ; 1.51 M 158-160 7.25 7.08 (m, 2H, 7.02 (d, J=10.0 Hz, (M+) HT), 4.04 (bs, 2H), 3.18 (hept, J =7.0 Hz, {H), 1.44 — 1.24 (m, 6D) (CDCls) 8 10.05 (s, 1H), 8.95 (5, 1H), 8.60 (s, ITD), 8.30 = 8.21 (m, 2H), 7.99 (s, 1H), 544 7.85 7.73 (m, 411), 7.44 — 7.37 (m, 2), 1-52 C . | 220-223 | 7.34 (d, J = 7.9 Hz. 1H), 7.24 (ud, J = 8.1, (IM+H]) 5.8 Hz, 11D), 7.05 (ddd, J = 11.1, 8.2, 1.3
Hz, 1H), 3.37 = 3.21 (m, 1H), 1.41 (dd, J = 7.1, 1.2 Hz, 6H) (DMSO-dg) 8 11.98 (s, 11D), 10.11 (s, LI), 9.57 (s, 1H), 8.24 8.19 (m, 3H), 8.19 — 8.14 (im, 2H), 8.09 — 8.03 (m, 2H), 8.03 — ) 7.96 (m, 210), 7.39 (dd, J = 8.7, 6.4 Hz, 1.53 c 527 LH), 7.22 = 7.08 (m, 2H), 3.12 (hept, J = (IM+HM 7.1 Hz, 1H), 1.19 (d, J = 6.8 Hz, 611);
NMR (376 MHz, DMSO-d,,) 8 -60.81, -117.72
:
Iyy 13 19
SiS m I, C,or "F NMR nD Synthesis MS ’ P y
Metho (°C) (8) (DMSO-d) 8 12.07 - 11.88 (m, 1H), 10.11 (s, 111), 9.45 (s, 11D), 8.21 (s, 1H), 8.18 - 8.13 (m, 2H), 8.13 — 8.08 (m, 2H), 8.08 —- 8.03 (m, 2H), 7.67 - 7.39 (mm, 2H), 7.39 503 (dd, /=8.7, 6.5 Hz, 11), 7.22 — 7.08 (m, 1-54 C - 2H), 3.12 (hepl, J =7.0 He, LHD), 1.19 (d, J ; (IML) = 6.8117 611); “1 NMR (376 MHz, DMSO-d) 5-85.19, : -86.92, -117.73 ; (CDC) 88.64 (d, J = 1.1117, 111), 8.09 (m, 3H), 7.93 (m, 3), 7.78 (d, J = 8.5 llz, 402 3H), 7.30 (d, J =7.9 Hz, 3H), 2.42 (s, 4H);
I-55 p* [M-HT)
PF NMR (376 Mtiz, CDCl) 8-75.61, - 75.63, -75.63, -182.14, -182.17, -182.18 (CDC13) 8 10.09 (s, 1H, 8.71 (s, 1H), 8.39 : (d. J =8311z 21), 8.01 (d, /=8.3 Hz, 2H), 7.95 (m, 2H). 7.82 (d, / = 8.6 He. « 418 2M);
I-56 p* (IM+H]Y)
YF NMR (376 Mz, CDCly) 6 -75.57, - 75.59, -182.14, -182.16, -182.18 : (DMSO-ds) 8 11.98 (s, IID), 10.11 (s, HID), 9.54 (s, LH), 8.30 - 8.20 (m, 311), 8.19 - 8.13 (m, 2H), 8.10 = 8.03 (m, 2H), 7.93 (d,
J=8.5Hz 2), 7.39 (dd, J=8.7, 6.4 Hz, : 627 1H), 7.21 = 7.08 (my, 2H), 3.12 (hept, J = : 1-57 C - 6.7 Hz, 1H), 1.19 (d, J = 6.8 Hz, 6H); : (IM+H]")
YH NMR (376 MHz, DMSO-dg) 8-75.08 (d.J=74 Hz, -117.73, -179.04 --182.36 : (m) :
lyp 13 190 ny aia m : HH, C,or "'F NMR i nD Synthesis MS
Method QP (8)! (CDCl) & 8.65 (5, LH), 8.10 (m, 2H), 7.93 (m, 2IN), 7.77 (d, J = 8.3 Hz, 21D), 7.30 (m, 2H), 2.42 (s, 3H); 454 on. oo 1-58 p= . °F NMR (376 Mllz, CDCl3) § -73.89, - (IME) 73.91, -73.92,-73.93, -73.94, -73.95, - 73.95, -73.97, -73.97, -79.19, -79.22, - 121.15, -121.18, -121 41, -121.43, -121 .44, -121.46, -182.85, -182.87, -182.89, - 182.90 (CDC) 8 10.09 (s, (11), 8.72 (s, 1H), 8.39 (my, 2D), 8.01 (m, 21D, 7.95 (m, 2H), 7.30 468( (d, J=28.3 Hz, 2H); 1-59 p+ . [M+HTH
Pr NMR (376 MIlz, CDCly) 8-73.84, ; 279.18, -121.08, -182.84 (DMSO-dg) & 11.98 (s, 1H), 10.11 (s, LH), 9.55 (s, LI), 8.31 — 8.20 (m, 311), 8.20 — 8.13 (m, 2H), 8.11 ~ 8.03 (mm, 2H), 7.92 (d, ;
J=8.5 Hz, 2H), 7.39 (dd, J = 8.7, 6.5 Hz, 1H), 7.23 = 7.07 (m, 211), 3.12 (hept, J =
C 677 6.7 Hz, 1H), 1.19 (d, J = 6.9 Hz, 6H); (IM+HTH "*F NMR (376 MHz, DMSO-d) § -73.44 (did, J = 15.4, 8.1,7.5, 3.0 Hy), -78.73 (d, :
J=12.8 Hz), -117.73, -120.00 - -122.33 (m), -182.26 (tt, J = 12.8, 6.4 [17) (CDCI3) 88.61 (s, LH), 8.11 (d, J = 8.16 3 Hz, 2H), 7.84 (d, J = 8.68 Hz, 2H), 7.67 (d,
I-61 p* (MIT ) J = 8.68 Hz, 211), 7.30 (d, J = 7.96 lz, 2H), 2.43 (s, 3H), 1.98 (¢, J = 18.12 Hz, 3H) » (CDCl) 6 10.11 (s, 111), 8.69 (s, 111), 8.41
RT a Q _ . 3 162 pe 130-141 «@ J =38.28 lz, 211), 8.02 «@ J = 8.28 Hz, (IM+H]") 2H), 7.87 (d, J=8.56 Hz, 2H), 7.71 (d, J = 8.56 Iz, 211), 2.00 (t, J = 18.12 Hz, 3H) ;
Synthesis mp "I, °C, or "F NMR nD DIMAS: MS
Method (°C) (S)' (DMSO-dg) & 11.98 (s, LHD), 10.11 5, LHD, 9.49 (s, 1D, 8.21 (d, J = 0.8 Iz, [I]), 8.16 (d, J = 8.4 Hz, 2H), 8.12 — 8.03 (my, 4H), 7.85 -7.76 (m, 2H), 7.39 (dd, J =8.7, 6 4 523 Hz, 1H), 7.22 = 7.08 (m, 211), 3.12 (hept, J 1-63 C . = 6.0 Hz, 1H), 2.04 (1, J = 18.9 Hz, 3H), (M+) 1.19 (d, J = 6.8 Hz, 61D); 1 NMR (376 MLiz, DMSO-d) 8 -84.18, -117.72 (DMSO-ds) 3 12.04 (s, TTD), 10.17 (s, LH), 9.62 (s, LH), 8.30 (d, J = 1.6 Hz, LH), 8.28 ] (d, J=4.6 Hz, 2H), 8.25 — 8.19 (m, 2H), ; 8.17 -8.08 (m, 2I1), 8.01 (d. J =8.6 Hy, 577 2H), 7.45 (dd, J = 8.7, 6.4 Hz, 1H). 7.27 -
C . 7.12 (m, 2H), 3.17 (hept, J =6.9 Hz, 1H), : (IM+H[") 1.24 (d, J = 6.8 Hz, 611); ""F NMR (376 MHz, DMSO-dq) § -84.03 (d, J=26Hz),-113.43,-117.72 (DMSO-d) 8 11.92 (s, LED, 10.05 (s, LHD, 9.57 (s, 1H), 8.29 = 7.94 (m, 9H), 7.20 (ddd, J = 20.5, 9.6, 4.3 Hz, 2H), 7.06 (td, J 527 =8.4,3.0 Hz, 1ID), 3.18 = 3.03 (m, [H), :
I-65 C CT 1.19 (d, J = 6.8 Hz, 6H); (IM+H]")
F NMR (376 Mllz, DMSO-dq) § -60.81, -114.66 :
NMR spectral data were acquired using a 400 MHz instrument unless otherwise noted. :
P* — Prepared according to methods described in Crouse et al. PCT Int. Appl. Publ. WO2009/102736 :
Al and Brown, et al, WO 2011017504 Al.
Table 3: Structures for Compounds /~=N [ ;
N A N oo OL LT
FF Noy Ay :
oN ) cl
On
ZU F “ oa. Noy
Cl
JN : ww cl 3C hata “OOS ‘ F x i
FF Nyy cl
ON Bat «| LO
FF NNN :
F
/~N :
N ha ~ TF i 5C A N S ;
F &
FT Nyy :
OH : “QL /=N “LOMO
F a i
FF Nyy
F
F : ~N 7C ON S oy. ERS
TF
So oc ON T ; - oN,
S :
FF NN : = /~N ~~ o-{ Or ACT 9C bd N S
FF NA :
NA QL
10C Fats “NOL 3
F
Fo Noy Ay ;
F ne | oO “OL S
FF Nyy ; 0 : \ /~<N OL
FA s
Fr Ney
Q :
HN-$ re
F = : 7; Nyy
N-S
Lac Na 94 ) o-{ NZ . S
FA OL AN bs :
NTN
. /~N NY 15C N. L 7 N CA
F UNL
FF NN :
Ni ; :
Nh P=
FF Nyy i
0 3 yO TL ec OA 5
FA
FF ye 0
OF
A TTL
15C Oy S
FA 7
LF yd JJ
J
N- 7S /~N pg ——
FA “OL )
FF Nyy ,. /~N Oo _ 200 o-{ IN B
FA N $
FF Noy 0 o
JN o-{ : “CL S 21C N S
FA nL 0 Co /=N 0 220 Fatal Ng
FA, Nog 0 N oJ /~N YY hg : 23C 0-4 I, 00
FA IID
NN 0 24€ Fabs “OL Ng
FP Ny 9
NR
25C oO “OL Sy
FP NNN
0
JN Na ;
FE NNN
]
Nar NE vel 2a
F FE Nog oy ro LJ ~ Nh 0 Y 0 :
EON oo ¥ FF ANN % ~N NOU 29¢C ON Ns oN :
FA Noy An 0 N. 0 ry YK :
No 0 ;
Br J: ANNE : 0,
No) T ! 3 Or “CL oS "Fr Nyy : 92 i
0
JN To me | 0
F -
FF Ny :
Cl oA :
ON T°
I ;
FF Ng Ay
Cl 0, (
NN & we |p MOLTO
F PN
FF Noy
Cl
NA o 35C Fala “CL N—s
F - oy-k !
NA Oo «| ON
FA No Ay «= «3 © ;
Owl S : 37C ~N = :
Fr Na
FF ry
OF on TF O— ; - N. =~N ]
E MO
NAT a
0 F on A= TF 39C ~N Os he
F 2 at
SOYA
F 0 on Ow 40C JN Oy ps ;
F N Ny" ©
Bor so
NO
0O-_-S § 41C =N »
I» NN ; 1,0
So on g 0 42C ~N sy S .
N. —~ rf ory A
Fo
BONS
0 : 43C _N bs
ROY
LAT
70
O o— 5D 440 N OS \
CoO :
LT
FO be 0
O~ N UO 45C OS,
N { )- V4 [J 0
I F i o- ;
O_-S 46C AN No 0"
N : nL 0
Fr /<N HO~©
Ley = 47¢ $ :
FA
A eh
JN Ho 450 oO “OL LO
FF Nyy - o~( } SN :
I N :
Fh N= "° 49¢ Fg 5 “AL
SN HO 0 ; nN" 50C F . T 0,
AF N A \ !
F EB ‘N SN : /=N HOO od = §
F IF _~N. 7p NTN
0 PT /~N HO ol OS P
FA
Fr Nyy o NO oo| FOND
FA S
/~<N Ho” wo| Oe GP ¥ Nx :
FF Nyy : 0 : /~N v=
F s :
FE Nog : “0 N 0 :
A
56C . NC ny el N. IS ° N NSN
Sg 7 No N—¢° 57C i ~N q
F ’ N_/ . tod mn a
AY
530 ON "
Fal “OL S
F
FF Noy :
0
Soy 0
HO
59C N nA oA “CL L
FA ANNTN
EF
} 2~0
EN J 0 60C oy
FO Sx
FA NA
J oN NO 61C LH T
A “CL S
FFE Nay Ay
CF;CO,H
N 0 /~=N N
FA 5
CFCOH HN
HO 0 /=N 7 NA wo) OAS
A SI
CEICOM, /~N he N-© :
KF £
FF Noy
CF;CO.Il HN /~=N RG we Ny LO
CFCOH 7 /=<N Yoo " ON 5
FA WL
CF;CO,H mo 0 a "Ce
Ol
F FF Nog
Na”
SN or’
Fy Nay
FF - 0
Pod YA J 69C “OL SN ~N-N 0”
FO O
70C N {OH R, \N De
E_o 0 :
ERO TL
71C ¥ oN wd FN - N-N
Fo O
CL $Y 720 NNO
~N S 73C | kf oy /
FO
F
F=-0 —
M
N-N
N=
SO =
F
F440,
Q {- 75C
SL N 3
N-N N y 3 : 8 Ne : “NO ~ Ts
Sy oN N os LT 1), Oy : 76C N-N S \ 4 52
P40 SR =
F4-0 {
F 0 So OH : 77C :
UN N=]
On S :
F F
F140 pF : gs XY 78C A ©
N-N 5
N=
SO ~ :
E
F-4+0,
Root 79C F
N-N OT
SO = S
F 0
FO ;
F
80C Y In :
N-N OH ; 3 N=
HS
8IC | F_O N AT ~
P< N N \=N 82C F. OQ N N ~ :
FX NOS N : 83C ROO JA hd
Fp No N , : 0 :
AS Cl 84C | FO N ~ \=N
Ci 0
A :
FO N \ 85C heft AT oO { \=N :
ue
N
0 ~X eo; AON ea be \=N
F ; eg
OF N ht 87C F NOS N :
NA
FF MON
LT ~ 89C -~ 0)
LO 0
F 0 ~ i LON 90C : ie "y 5
Np Wn
LAT
4 91C nS *y ©
F : ON
LY A : ve o
FO
2 or . i N ‘ 3C . IN Y }S
F OL I
HAT / :
94C Ie dy 0 / 0
Cl . 95C N Oi N
EN, Y
E Ru PW F
HALT
0 960 IS N
F SOL :
HAT
O \ ~~ No : 97C ~~ I
FF yO : 0
Fr pa 0
Pod HN : a 0
POG HH
_N-N 0 :
J uN: Oo
Pod 30 ~ Br 2N-N
Br ;
F_T “ O :
FF 7=N 100C Eats A
N-N
FF - 0
Pod A 1 101C “OL yr :
SN NOT :
FF /~=N o
EX N= ~~ a 102C 0 “CL 0) _N-N
Ct :
FF 0 osc | For “Yo 24
LT
_UN-N
FF Ne 0
FOB
Yr
ZN-N : he ~~ ~ :
F No / 105C or “CL Yr ~N-N ¢
Cl _ — o : 106C Oey A { y 0
N-N
EF JN 0 O o ; ore | Tor OL “4 )
N~N rr — 0 ose | For OL Se) : y ~N-N : 0 0—
FF 0 °1
Cl : 00
FF 0
LOC P<, LH at
FF - 0 [rc Po NA Jt
N-N
FF ~N 0 gX N ~{ : 1120 o-{ Nv" SN
FF /~<\ 0 113C Pod IN i. : : Y
Ls N=N :
F. F /~N 0 nae | For OL CA
Lx ;
NAN o
EOE O isc | Ff OL oh . bd E
N-N 0, 0-
NE /~=N —¢ om nec | Ff od 2 SN ¥
NN
FOF - 0 “ od NA —~{ 117¢C N SN »N-N N | :
EF 0 xX 9) r~ : 118C Fo pe SN
SN-N x
FF 0
OE
119C 0 NJ § ;
OL
~N-N
O
F /~=N ~~ 120C —{) ™ s ~N-N ;
FF - 0 121C FX NA ~ ] 210 0 “OL SUN g ¥ ~N-N
FF ~ 0
Pod INA JT 122C N vo
N-N t /~N —~ 123C oo) SN #N-N Nx :
ST
EF ~~ 0" F
N-N pF UY ‘ : $7 N=0
PO gd 125( NY
FE /~N :
Hod YN §7N=0 126C wan o—<" = . he! =X ° 127C o-{ N” S\N wr :
FF . 0 : x A) ( gc | Fo Ny SN :
N-N : = N O
Po fH oo
ANN
NE dy
Xe NAD ~ 131C od) N SUN : : vr :
NAN
FF No . od HN JL 132C N yw :
N-N . :
FEF ~ 1X LH JL 133C 0 N SN
NN
F /~N 134C a No 4 . F : bd _N-N
FoF /=N 0 7 SON _N-N
FOF JN
BX N /\ : 136C oN SN
N-N
FOF /~N
Pod IN - {XN 137C “OL Yr :
N-N 0 \
FF - od NA BY 138C “CL r _N-N
Q : \ é
FF Nl 3
FX LNA Qo 139C 0 N SN ~N-N g et JN fa o— 140C ov SN _N-N
FF —_ —_ 141C f o-{ IN, SyN ~N-N :
FF —_— 142C N SN
N-N :
For Z
MOD OS
143C “OL 0) ~N-N : r :
FF /~N ( aac | PG) 2 SN _
F_F ~N ;
Pod Nd dN _N-N :
FF - 1X LH M9 _N-N
EF ~\
Ba {HA / : 147C © N SN 0
FF ~
Pod YN JA
Cat 0
NAN
F
F. F — F F 149C Po) VA NA
OL
N-N
Cl :
RF 7=N 0 S
EF /~N ~~ ~N=-N ;
F
FF — pa 152C Pod A S\N 7 “ou _N-N
F
FF oa MF ; 153C od SN LF _N-N :
: §
PX NT) ~ sac | Pol) OL 2N-N
I F rN - : 7 2 NN
SPN
(56C Po) SOL A _N-N :
E F /~N J cl : 157C Oy SUN - = N—N ;
Cl
FF — . Cl
FOr 47 158C N N
Tar _N-N jv /~N
F
159C “Oy _N~-N
F
DC N ~ ’ 60C | © a JN vv
N-N i
Ci : xr oN ~ 0 ny P S :
N-N
EF = :
Po ONAL CX 162C “OL Y _N-N : 0 : nF NN ~ 0 - S : 163C L “OL SN
FF { 164C | Fo NE S F “CLO _N-N
EF /<N ~
OI
165C N SN _N-N
FF
NO
166C N yN _N-N
FF ~N ~c
Pod Yn B g Cl 167C N oN _N-N
E_F f 168C Pood HNN ad a
CLO
LN-N
FF — FF od YA ~( Yr 169C N Sy-N
NN
L
FF - F 170C Pod HN ~~ QF “OL r 0)
N-N
IF /~N ~ ] : Pod YN B = I 171C N SN
NN oF /~N —
Pod YN ~~ 1720 Y
LN—-N o \ i
EF — 173C Po A TG “oud ~N-N :
FF —-
FOIA A K
174C “OL >
N-N
Cl
FF —
FX LO ~ 175C 0 N SyN
N-N
FF —
FX LNA ~( 176C © N SON
N-N
FT —_
FX NN g ) 177C © N »N
N-N ve <N ~ 2 PoL Ny Sy 178C ed =
F /=N /\
Or SN 179C F JR =
FF /~N
Pod YN SN, ] 180C a —
AF /~N —
FX LA S g © N N : 181C Lu 0—
EF /~N !
IRC Pod DN, NN 82C =
FF /~N
PX LH J S
O = h ~N-N
FF ~~ oo
Pod YN g ) 184C ly ii /<N
Pod I Sy 185C “OL N
FF wt :
SoA ~N=N
FF -
Pod HN Ss ) 187C “OL Na
N-N ; “5
FF NC od YN A ) i N 188C : OL Nc ~N-N <0
NF FN ~ :
F N : oH S 189C “OL NF ~N-N —~
Ne" /=N
Pod YN S ) F 190C N F :
SN-N F cl iv /<N
FX AH i 0 N= SE : -
Ee
FF /=~\
X N g % N yl 192C JN-N &S 0— i /=N
N S od) \@ \ 193C or ~
BF /=N £X LHX B S ) {3 194C wr?
BF /<N x \ ;
Fo Ne . J 195C NN ,
EF /~<N
X N $d) 196C J
Cl eT /=N — o-L N” N ~( 197C NN eF SN J
F or N* VN 198C JRVRY _
N § “oO YN od 0 F
FF ! od HN 5 ) F i N . 200 OL 0
FF x ~=N 201C OL FN FS
NAN
Cl
N {3 202C | pF Ot
Po 7
OCH, =N {3 : 203C | or ST
LT 7
Br —N {3 OCH, 204C FF N. 2 x
SL N MN
IN $3 205C ¢ J TN 7 iN ~N
LLCO 0)
FO N
\ 0 2060 Wi Ko r
Ll N N- :
LAT ~O- 0
HCO
N {) 207C | OY
Fo }
CO,Et
FoF AN
Pod HN sO) : 208C CN om
N-N 9
F ~N i 4 50 209C No] S kJ /~N
LO 0 210C Ne
RF /~N
OT
IC N aN oF /~<N
Pol YN ) - N 2120 JR oS ~F /~N TN ’ od )- SN 213C Ned —
FF /~<N —
Pod YN s i 214C J Ke
RF /~<N —~
Pod ye iu EF = N 215C ed 7
Cl
FF /~N
F Sod) = $Y 216C N No
FF /=~N
F Oy 5, Fo 217C CON F
UN-N F ;
FF ~=N a 218C Pod TO
: /~N Sr
FE N. YN 219C Fo N N-N 5 = . ~N {) } FV J) SN 220¢ Po IOUS . ~N dr Ff 1 I” No rN 0, “=~ Fo N _N-N CS
FF ~N <r {Fo 17230 ~=N 223C ; iD nL
Fo
N Lr 224C i. J rr
Fo [0 =N NN
Noy N-
AT yO . | F = : N _
SK AT 7 F [NO
S
227C Cr J
IO Fe 228C a. I) rN_F
Fc Lr Na PWN
FO
:
I
229( . I NOTE [DL 3 SO )
X,Y 7
QO
N {or 2300 . F J re « N-
LY ~Co
O
EEO
231C FF Or 0 ’ /
O—
QO
\ Lr 232( i J r
FF IaPWE
AT
O ;
N {or 0 233C . r= rr I
F "0
Q
$F 234C = ae
OO)
FO
FO “ 235C ~ rN
HOOD
FO
N sr? 236C ~ rN
REIN
F "0
N rv 237C r rN
EI
FO u at 238C r~ rN
FO :
0 $Y 239C : = rN
Fog OO
FO 7 /~N
Woh 3 soc | To ee ~N ; “CL :
LOMB
241C | Fb Ne? /~<N 1, 0A sane | 0 Ney?
O— 7=N
F N PY
243C | F J @ =
So N-NZN /~N
N, = S b
F N 3 244C ANG] Nap? Cl 2 /~N : : “CL : 245C to Ney Pn F : 28
~N
NJ S
LO ; 246C P50 Ne? Cl /~N
NJ) S
OLA
247C Po 3S
Fl
I
/~N
N. S
We ;
F ~# 243C | Fg ane ~N $4
Oren 249C 0 7 "N
F0
F
FF
FX {ra
O NZ
250C OL > - ’ NPN =
F F
HO
251C “NOL 23
FF : i “OL > 252C Noy Zn 2
} iD
Tew . FF
FN /~=N
N S
“1 [ |] 253C NLA ) oO
F F
0) = 254C N >
NA g F /==N ¥ { ) N ; ¢ S 255C J
NA a i r F oO 256C >
Nod -~ F
F F /=N : ' OL 257¢ | FF >
F NA]
I? a - — i
EEO
258 | F&F > : Nd :
: : ; 7~N
N S i 259C NA]
NE fx F C oN ‘NT S
F . 260C OL 7~N
LO OL
N S
F iP
UN. A 261C N :
F
Table 4: Analytical Data for Compounds in Table 3 pp | Synthesis MS | mp (°C) 'H NMR (3)’
Method pt (DMSO-d) 8.61 (s, LF), 8.43 (s, 1H), 8.22 (d, J = 8.24 Hz, 2H), 8.17 (s, LH), 7.89 (d, J oo = 8.24 Hz, 2H), 7.80 (d, J = 8.28 Hz, 2H), 1c D 340 (M+) 741d, J = 8.28 17, 2H), 7.19 (d, J = 8.24
Hz, 210), 6.71 (d, J = 8.24 Hz, 2H), 2.99 (s, 6H). 2.42 (s, 3H) (DMSO-d) 9.42 (s, 1H), 8.18-8.03 (m, SH), . 3 7.78-7.69 (m, 241), 7.61 (d, J = 8.26 Hz, 2 ( _ d, ¢ b S80 (MH) | L68=1TL | ory 9 4d (4, T= 8.24 Hy, 2H). 7.18 (im. 11), 3.09-2.99 (m, 2H), 1.39-1.32 (m, 3) (DMSO-dq) 9.42 (s, LH), 8.18-8.04 (m, 5H), 7.78-7.69 (m, 28), 7.61 (d, J = 8.26 Hz, ; 3C nD 504 180~182 | 211), 7.48 (d, J = 8.24 Hz, 2H), 7.19 (m,
LET), 3.06-3.02 (m, 20), 1.78-1.64 (m, 211). 1.04-0.96 (m, 3H)
: :
Synthesis . o | i
ID Method MS mp (°C) IINMR (§) (DMSO-dg) 8.57 (s, 1H), 8.48 (d, J =5.5
Hz, 1H), 8.22, J=8.2 Hz, 2H), 7.91-7.75 4C D 629 (M+) (m, 50), 7.38 (d, J = 8.7 Hz, 2), 7.22-7.07 (mi, 31D), 6.50-6.19 (m, 2H), 3.85(d, J =7.2
Hz, 111), 3.75-3.64 (m, 1), 2.33 (s, 611) (300 Mllz, CDCI3) 8.36 (s, 1D), 8.54 (s,
IH), 823 (dl, /J=83 Hz, 2H), 789d, J = 5C FE 636 (M+) 8.2 Hz, 3M, 7.79 (4, 7=9.0 Hz, 211), 7.38 (d, J =8.7 Hz, 2I'D), 7.23-7.00 (m, 4L1), 6.88- 6.74 (m, 2H), 4.44 (s, 2H), 2.33 (s, 6H) (methanol-dy) 9.16 (s, LI), 8.46 (s, ITD), \ 645 0h 8.21 (d, J = 8.3 Hg, 21D), 8.03 (m, 611), 7.52 6C (M+H) 196-198 (d, J=8.3 Hz, 4H), 7.28 — 6.91 (m, 3H), 4.39 (s, 210), 2.08 (s, 611) (300 Ml1z, CDCI) 8.56 (my, 2), 8.23 (d. J = 8.3 Hy, 2H), 7.88 (d, J = 8.3 Hz, 3H), 7.79 7C I: 636 (M+) (d, J=9.0 Hz, 21), 7.55-7.42 (m, 111), 7.37 (d, J =9.0 Hg, 21D, 7.20-7.01 (m, 311), 6.89- 6.68 (m, 2H), 4.30 (s, 2H), 2.28 (s, 6H) (CDCl3) 8.57 (s, 1H), 8.52 (s, 1H), 8.24 (d, J . . =8.3 Hz, 2H), 7.91-7.84 (mm, 3H), 7.80 (d, J 8C E 634 (M+) = 9.1 Hz, 2H), 7.39 (d, J = 8.6 Hz, 4H), 7.18-7.03 (m, 511), 4.32 (s, 211), 2.29 (s, 61) (CDCl3) 8.57 (s, 11), 8.47 (s, LID), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.80 9C E 620) (M+) (m, 3H), 7.39 (d, J = 8.4 17, 21D), 7.21-7.10 (m, 3H), 3.93 (s, 2H), 2.35 (s, 611). 0.13 (s, 9H) (DMSO-d) 8.57 (s, LI), 8.54 (s, 111), 8.23 (d, J =8.3 Hg, 2H), 7.89 (d, J = 8.3 Hz, 2H). 10C D 600 (M+) 7.87 (s, 1H), 7.80 (d, J = 9.0 Hz, 2H), 7.44- 7.32 (m, 411), 7.31-7.19 (m, 3H), 7.19-7.00 (1m, 3H), 4.34 (s, 2H), 2.31 (s, 6H) (DMSO-de) 8.57 (s, 1H), 8.55 (s, 1H), 8.23 (d, /=8731lz, 210), 7.89 (d, J=8.3 Hz, 21D), 11C 618 (M+) 7.86 (s, LH), 7.83-7.73 (m, 2H), 7.48 (1d, J = 7.6, 1.7-Hz, ITD), 7.38 (d, J = 8.5 Hz, 2H), 7.23-6.91 (m, 6k), 4.39 (s, 211), 2.30 (s, 61) :
Synthesis . 0 f 1 (DMSO-d) 8.57 (s. LH). 8.51 (s. LH), 8.23 (d, J =8.3 Hz, 2H), 7.94 (d, J = 8.3 Hz, 2H), } 7.88 (d, J = 8.2 Hz, 211), 7.86 (s, 111), 7.79 12C b 658 (M+) (J =9.0 Fz, 2H). 7.44 (d, J = 8.3 Haz, 2H), 7.38 (d, J = 8.6 Hz, 2H), 7.20-7.05 (m, 311), 4.35 (s, 2H), 3.88 (s, 3H), 2.28 (s, 611) (DMSO-d) 8.59 (s, LH), 8.51 (s, 1H), 8.23 (d, J = 8.3 Hz, 211), 7.93-7.76 (m, 711), 7.53 13C I 679 (M+) (d, J = 8.2 Hz, 211), 7.39 (d, J = 8.7 Hz, 211), 7.20-7.06 (m, 3H), 4.88 (s, 2H), 4.36 (s, 200), 2.28 (s, 611) (CDCly) 8.57 (s, 111), 8.52 (s. LE), 8.23 (d, J = 8.3 Hz, 2H), 7.91-7.85 (m, 4H), 7.80 (d, J . = 0.1 Hz, 210), 7.73 (d, J = 6.8 Iz, LID), 7.52 14C E 658 (M+) (dd, J= 8.8.69 Hz, LH), 7.39 (d, J = 9.0
Hz, 2H), 7.13-7.01 (m, 3H), 4.88 (s, 2H), 2.27 (s, 611) (CDCl) 8.57 (s, 1H), 8.25-8.14 (m, 3D), 15C E 667 (M+) 7.94-7.66 (m, 7H), 7.52-7.35 (m, 6H), 7.16- 7.03 (m, 3H), 4.54 (s, 2H), 2.32 (s, 611) (CDCly) 8.57 (s, LH), 8.49 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.3 Hz, 2H), 16C I 658 (M+) 7.83-7.77 (m, 311), 7.39 (d, J = 8.3 [1z, 2H), 7.19-7.07 (1, 3H), 6.69-6.65 (m, 1H), 6.39- 6.35 (mn, 1H), 4.36 (s, 2H), 2.29 (s, 6H) ; (CDCl5) 8.58 (s, 111), 8.50 (s, 111), 8.23 (d, J =8.3 Hz, 211), 7.94-7.74 (m, 7H), 7.59 (d. J 17C RE 678 (M+) = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Fz, 2), 7.20-7.04 (m, 311), 4.37 (s, 21D), 3.01 (s, 3H), 2.29 (s, 6H) (CDCl3) 8.59 (s, 1H), 8.46 (s, 1H), 8.22 (d, J =8.4 Iz, 211), 7.86 (d, J = 8.4 [17, 211), 7.83-7.75 (m, 3H), 7.63 (d, J = 8.4 Hz, 2H), 18C FE 773 (M+) 7.44 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Ho, 2H), 7.17-7.05 (m, 3H), 7.03-6.98 (m, 3D), : 6.89 (1, J = 8.6 Hz, 2H), 4.30 (s. 2H), 2.24 : (s, 6H) :
ei (CDCLL) 8.59 (s, 2H), 8.26 (d, J = 8.3 He, 2H), 7.93 (d, J =8.3 Hz, 2H), 7.89 (s, LH), 19C BE 728 (M+) 7.82 (d, J=9.11z, 21H, 7.40 (d, J = 8.3 liz, 2H), 7.20-7.05 (m, 3H), 6.86 (s, 1H), 4.49 (s, 2H), 3.98 (s, 31D), 2.31 (s, 6H) (CDCl) 8.58 (s, IHD), 8.38 (s, 111), 8.23 (d, J = 8.3 Hz, 2H), 7.86 (d, J = 8.3 Hz, 3H), 7.81 20C FE 681 (M+) (d, 7=9.1 Hz, 21D), 7.67-7.63 (m, 2), 7.46- 7.36 (mm, SI), 7.18-7.05 (m, 311), 4.24 (s, 2H), 2.47 (s, 3H), 2.29 (s, 6H) (DMSO-de) 8.58 (s, LH), 8.15(d, /=8.4
Hz, 210), 7.80 (d, J = 9.0 Hz, 211), 7.47-7.35 21C E 596 (M+) (nm, 4H), 7.21-6.93 (m, 5H), 3.68 (t,.J=5.4
Hz, 21D), 3.35 (s, 31), 2.65 (t. J = 6.2 117, 2H), 2.29 (s, 61) (DMSO-d) 8.59 (s, TH), 8.52 (s, TH), 8.23 i (d, J =8.3 Hz, 2I1), 7.95-7.75 (mm, 5H), 7.39 22C E 626 (M+) (d, J =8.4 Hz, 21D, 7.21-7.06 (m, 3H), 5.80 (s, 2H), 4.12 (s, 2H), 3.69-3.50 (m, 2H), 2.31 (s, 6H), 1.35-1.11 (m, 3H) (DMSO-d) 8.38 (s, 1H), 8.50 (s, 1H), 8.22 (d, J=8.2 Hz, 2H), 7.93-7.70 (m, 5H), 7.45- 23C E 731 (M+) 7.28 (m, 81), 7.23-7.03 (m, 311), 5.79 (s, 2H), 5.38-5.27 (m, 1H), 5.11 (s, 2H), 4.07- 3.98 (m. 2H), 2.30 (s, 6H) (DMSO-d) 8.58 (s, 1H), 8.51 (s, LH), 8.22 (d, J =8.3 Hz, 211), 7.93-7.73 (m, 5H), 7.39 24 E 626 (M+) (d, J =8.9 Hz. 2H), 7.21-7.07 (m, 3H), 5.76 (s, 2D), 5.05-4.70 (m, 11D), 2.32 (s, 611), 1.38-1.17 (m, 6H) (DMSO-de) 8.59 (s, 1H), 8.52 (5, 1H), 8.23 (d, J=8.3 Hz, 21D), 7.91-7.79 (m, 51). 7.40 25C I 610 (M+) (d, J =8.5 Hz, 2H), 7.18-7.06 (m, 3H), 5.73 : (s, 2H), 2.70-2.45 (m, tH), 2.32 (s, 6H), 1.15 (s, 611) ;
wi
Synthesis o 1 yes MS | mp (°C) 1 NMR (8) (DMSO-dg) 8.58 (s. LH), 8.21 (d, J=8.4
Hz, 211), 7.98 (d, J = 8.4 Hz, 2H), 7.81 (d, J . : =6.9 tz, 211), 7.69 (s, LH), 7.40 (d, J = 8.8 2 3 26C E 654 (M+) Hz. 20D). 6.63 (s, 2H), 5.73 (s. 2H), 3.80 (s. 310), 2.64-2.53 (m, 111), 2.58 (s, 311), 2.28 (s. 6H), 1.17 (d, J = 7.0 Hz, 611) (DMSO-dlg) 8.58 (s, TH), 8.50 (s. 1H), 8.23 (d, J=8.2 17, 211), 7.88 (d. J = 8.3 Hz, 210), . oo 7.81 (d, J =9.0 Hz, 211), 7.74 (s. 111), 7.39 2 i 1 7c E 640 (M+) (d, J = 8.6 Hz, 2H), 6.63 (s, 2H), 5.71 (s, 211y, 3.79 (5, 310), 2.74-2.43 (m, 11), 2.27 (s, 611), 1.16 (d. J = 7.0 Hz. 6L1) (300 MHz, CDCly) 8.58 (s, TF), 8.48 (s. 11D), 8.22 (d, J =8.3 [1z, 211), 7.87 (d, J = 8.4 Hz, 2H). 7.80 (d. J = 9.0 Hz, 211). 7.74 28C E 761 (M+) (s. 1H). 7.45-7.28 (m, TH), 6.63 (s, 21). 5.78 (s, 211), 5.29 (m, 11D), 5.12 (s. 2H). 4.03 (d, J = 5.6 Hz. 2H). 3.79 (s, 31). 2.27 (s. 6H) (300 MHz, CDCl) 8.58 (5, 1D), 8.49 (s,
LH), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 9.0 Hz, 2H), 7.72 29C I 656 (M+) (s, 111), 7.40 (d, J = 8.7 Iz, 211), 6.63 (s. 2H), 5.78 (s, 2H), 4.11 (s, 2H), 3.80 (s, 3H), 3.59 (q, J = 7.0 Hz, 2H), 2.27 (s, 6H), 1.24 (t. J =7.1 117. 31D) (300 MHz, CDCLy) 8.60 (s, LH), 8.50 (s,
LH), 8.22 (d, J = 8.3 Iz, 2H). 7.88 (d, J = } ] 8.2 Hz, 2H), 7.82 (s, 111). 7.80 (d. J = 9.0 ( J Q / 30C E 697 (M+) Hz, 2H), 7.38 (d. J = 8.8 He, 3H). 7.23-7.02 (m, 3H), 5.78 (s, 211), 3.96 (s, 21), 2.31 (s, 611), 1.44 (s, OID) (300 MHz, CDCl5) 8.58 (s, 11), 8.52 (s, (H), 8.23 (d, J = 8.3 Fz, 2H), 7.88 (m, 31D), 31C 0 582 (M+) 7.80 (d, J = 9.0 Hz, 2H), 7.38 (d, J = $.6 Hz, 2H), 7.14 (m, 3H), 5.72 (s, 2H), 2.32 (s. 611). 2.09 (s, 31D)
(CDCls) (Mixture of atropisomiers) [8.61 (s), 8.58 (s), 8.56 (5), 8.51 (s), 8.37 (d, J=8.3 12), 8.23 (d, J =8.4 lz), 8.21-8.14 (m), \ 8.00 (d, J = 8.4 Hz), 7.89 (d, J = 8.2 Hu), 32C E 697 (M+) 7.84-7.77 (m), 7.45-7.35 (m): 1 1H], 6.94 (s, 2H). [5.87 (5), 5.80 (s); 2H], [4.12 (s), 4.1 1 (s); 2H], 3.83 (s, 3H), 3.69-3.44 (m, 2H), 1.38-1.10 (m, 3H) (CDCly) 8.57 (s, LH), 8.51 (s, 1H), 8.23 (d. J = 8.3 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H), 33C E 697 (M+) 7.83-7.77 (m, 311), 7.39 (d, J = 8.4 Hz, 2), 6.94 (s, 2H), 5.76 (s, 211), 4.96-4.77 (m, 1H), 3.82 (s, 3H), 1.30 (d, J = 6.3 Hz, 6H) (CDCl3) 8.57 (s, LI), 8.51 (s, [I1), 8.23 (d, J = 8.3 Hz, 2H), 7.92-7.76 (mm, 5L1), 7.39 (d, J 34C E 631 (M+) = 8.4 Hz, 2H). 6.93 (s. 2H), 5.73 (s, 2H), 3.82 (s, 311), 2.59 (m, IH), 1.17 (d,J=7.0
Hz, 6D) (CDCI;) 8.57 (s, 1H), 8.50 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.92-7.73 (m, 51), 7.38 (d, J 35C E 636 (M+) = 8.3 Hz, 2H), 7.20-6.92 (m, 3H), 5.72 (s, 2H), 2.94-2.63 (m, 1H), 2.31 (s, 6H), 2.02- 1.38 (m, 8ID) (CDCLy) 8.56 (s, 1H), 8.49 (s, LH), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.84 36C E 624 (M+) (s, LID, 7.79 (d, J = 9.0 Hz, 211), 7.38 (d, J = 8.4 Hz, 2H), 7.19-7.05 (m, 3H), 5.71 Gs, 2H), 2.31 (s, 611), 1.20 (s, 9H) (CDCly) 8.59 (s, 110), 8.50 (s, 111), 8.23 (d, J 601 = 8.3 Hz, 2H), 7.93-7.77 (m, 4H), 7.72 (s, 37C FE Ma1D) IH), 7.40 (d, J = 9.0 Hz, 2H), 6.63 (s, 2H), 5.71 (s, 210), 3.80 (s, 311), 2.68-2.48 (m, 1H), 2.28 (s, 6H), 1.16 (d, J = 7.0 Hz, 6H) (CDCl) 8.58 (s, 1H), 8.47 (s, 1H), 8.23 (d, J =8.3 Hz, 211), 7.87 (d, J = 8.3 Hz, 211), 7.81 : (d,/=9.1 Hz, 2H), 7.71 (s, LH), 7.39 (d, J = ; 38C EF 724 (M+) 9.0 117, 211), 6.64 (s, 2H), 5.76 (dd, J = 37.3, : [1.0 Hz, 211), 4.19 (q, J = 6.9 Fz, 1H), 4.14- 3.97 (m, 1H), 3.80 (s, 3H), 3.79-3.68 (m, [1), 2.27 (s, 61D), 1.47 (d, J = 6.9 Fz, 3H)
Synthesis . ° | ol
HD Method MS mp (°C) II NMR (§) (CDCl) 8.58 (s. 1H), 8.48 (s, 1H). 8.24 (d, J = 8.3 Hz, 2M), 7.87 (d, J = 8.3 Hz, 2H), 7.83 (s, LHD), 7.81 (d. J = 9.1 Hz, 2H), 7.39 (d, J = 39 E 694 (M+) 8.3 Hz, 2H), 7.23-6.99 (m. 3H), 5.77 (dd, J = 36.4, 11.0 Hy, 2H), 4.19 (q, J = 6.9 Hz.
LD). 4.14-3.97 (m, LI), 3.84-3.65 (m, LEI), 2.31 (s, 6H). 1.47 (d, J = 6.9 Hz, 3H) (CDC) 8.57 (5, 111), 8.48 (s. 111), 8.23 (d, J = 8.3 Hz, 211), 7.87 (d, J = 8.3 Hz, 2H), 7.80 40C E 654 (M+) (A. J=9.0 Hz, 2H), 7.72 (s. 1H), 7.38 (d, J = 8.4 Hz, 211), 6.62 (5. 211), 5.70 (5, 211), 3.79 (s, 311), 2.27 (s. 6H), 1.20 (s. 911) (CDCls) 8.58 (s. IF). 8.49 (s, 1H). 8.23 (d, J ~83 [12 211), 7.87 (d, J = 8.3 [1z, 211), 7.84 (s. 1H), 7.80 (d. J = 9.0 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H). 7.23-6.96 (m. 3H), 5.77 (dd. J
He P 670 (M+) =27.4, 10.9 117, 21), 4.07 (q, J = 6.9 Hz,
LH), 3.78-3.70 (m, LH), 3.66-3.39 (m, 3H), 3.35 (s, 3H, 2.31 (s, 6H), 1.42 (d, J = 6.9
Hz, 310) (CDCl3) 8.58 (s. LH), 8.48 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.87 (d. J = 8.3 Hz, 2H), 7.80 (d,J=9.111z 2H), 7.71 (s. 111), 7.39 (d. J = . Ny 8.3 Hz, 2H), 6.63 (s, 2H), 5.76 (dd. J = 27.8, a} y
F 700 (M+) 10.9 Hz, 2H), 4.07 (g, J = 6.9 Hz, 1H), 3.79 (s, 311), 3.79-3.70 (m, 11D), 3.63-3.45 (Im, 3H), 3.35 (s, 3H), 2.27 (s, 6H), 1.42 (d. J = 6.9 Hz, 311) (CDCl) 8.57 (s, LIL), 8.49 (s., 111), 8.22 (d, J = 8.3 Hy, 2H), 7.87 (d. J = 8.3 Hz, 2H). 7.79 sc . (d,. = 9.1 Fiz, 211), 7.74 (5, 11D), 7.38 (d, / = 666 (M+) 8.3 Hz, 211), 6.62 (s, 211). 5.71 (s. 211), 3.79 (5. 3H). 2.85-2.65 (mn. 1H), 2.27 (s, 6H). 1.98-1.51 (m, SH) (CDCly) 8.59 (s. 1H), 8.55 (s. 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz. 2H). 7.84-7.74 (m, 3H), 7.38 (d. J = 8.4 Hz, 211), 44C I: 668 (M+) 6.63 (5; 2H), 5.85-5.73 (m, 211), 4.54-4.47 (m, 1H), 4.03 (dd, J = 14.7, 6.9 Hr. 1H), 3.91 (dd, J = 13.8, 7.4 Hz, 11), 3.79 (s. 311), 2.27 (s, 611), 2.09-1.83 (m. 4H)
i
Synthesis . 0 mete MRO (CDCL) 8.68 (s. LH), 8.49 (s. 1H). 8.24 (d, J = 8.3 Hy, 2H), 7.93 (d, J = 8.4 Hz, 2H), 7.88 . . 746 tao | (dS =8.3 Hz, 211), 7.81 (d, J = 8.5 Haz, 21D), 45C E MH) | PET 773 (5 1H, 7.35 (s, SID. 6.64 (5, 2H), 5.78 (5, 211), 5.24 (s, 111), 5.12 (s, 21), 4.04 (d, J = 5.5 Hz, 211), 3.80 (s, 311), 2.28 (s. 611) (CDCl) 8.68 (s. 1H), 8.50 (s, 1H), 8.24 (d. J = 8.3 17, 21D), 7.98-7.69 (m, 711), 6.63 (s, 46C° I 624 | 10S=113 | 21D), 5.71 (s, 2H), 3.80 (s, 3H), 2.59 (heptet,
J=7.0Hz, 1H),2.29 (d, J = 6.9 Hz, 6H), [16 (d. J=7.0 117 611) (acetone-dg) 9.20 (s. LHD, 8.52 (s, 1H), 8.40 — 8.21 (m, 2H), 8.21 —8.01 (im, 4H), 7.61 (d, 47C E 49-151; 8 3 Hy, 211), 7.32 — 6.94 (m. 311), 3.83 (s. 2H, 2.34 (s, 6H) (acetone-dg) 9.18 (s, 1H), 8.83 (s, 1H), 8.67 599 , ~7.82 (m. 81), 7.60 (d, J = 8.4 Fz, 210), sep EF an | 257 6.98 (5,211), 3.99 - 3.72 (m, 31). 2.41 = 2.20 (m, 6H) (methanol-dy) 9.23 (s, LIT), 8.62 (s, LH), . 619 ec | 8.29 (mn. 2H), 8.17 ~ 7.98 (in, 4H), 7.60 — 4C E M+) | 785 1945 (ml 2H). 7.41 — 7.19 (m. 3H), 4.22 (5, 201), 2.34 (s, 611) (methanol-dy) 9.23 (s, LI), 8.57 (s, LHD), 635 8.28 (m, 3H), 8.09 ~ 7.98 (m, 4H), 7.50 (m,
S0C E MID) | P9396 a a (9 — ant (m. 21h), 3.85 (s. 3H), 2.36 (s. 310) (methanol-dy) 9.23 (s, TH), 8.60 (s, 1H), , . 649 B 8.30 (m, 21D), 8.14 — 8.00 (m, 4L1), 7.52 (m,
SLC E Mk) | T0779 [apn 6.81 (5. 2H), 4.22 (5. 2H), 3.84 — 3.81 (m, 3H), 2.33 (s. 6H) (methanol-dy) 9.21 (s, 111), 8.44 (s, 111), 8.27 (d, J = 8.1 Hz, 211), 8.09 — 7.98 (mm. 599 4H), 7.52 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 2 g _ i 52C F Math) | OTT en 20D. 6.97 (d. J = 8.8 Tz, 211), 5.40 (s. 1H), 4.37 — 4.13 (m, 2H), 3.79 (s. 3H). 1.79 (m, 3H)
Synthesis o (methanol-dy) 9.21 (s, 1H), 8.44 (im, LH), 617 8.28 (d.J=82 Hz 2H), 8.11 — 7.99 (m, 53C I (MLD) 168-170 | 41D), 7.52 (d, J =8.4 liz, 2I1), 7.25 (m, 21D), “7.14 (t, J =8.5 He, 1H), 5.42 (m, LH), 4.25 (m, 21D), 3.88 (s, 31D), 1.75 (m, 3D) (mecthanol-d) 9.23 (s, 1H), 8.46 (s, LID), ) } 569 8.27 (im, 2H), 8.05 (im, 4H), 7.57 - 7.39 (m,
MC FE an | 71700 arn S41 (nn), 4.24 (m, 211), 1.79 (m, 31D (methanol-dy) 9.12 (s, 1H), 8.46 (s, 1H), 8.14 (m, 2H), 7.99 (m, 310), 7.78 (s, LID), - n 624 q 7.49 (d, J = 8.5 He, 2LD), 7.12 (m, 31D), 3.69 35C E M+) | 2007 | (6 2m), 3.222 2.80 (m. 2H). 2.25 (s, 6H), 2.03 (s, 2H), 1.93 — 1.66 (m, tI), 0.92 (m, J = 9.7 Hz, 61) (methanol-dy) 9.18 (s, 1H), 8.59 (s, 1H), 8.30 (d, J =8.1 Hz, 2ID, 8.12 (m, 2IT), 8.07 — 8.00 (m, 2H), 7.58 = 7.43 (m, 2H), 7.33 765 (dd, J=86,65Hs, 1H), 7.25(d,J=76
I6C E +n | Sn om, 4.02 (m, 211), 3.97 — 3.75 (m, 2H), 3.21 (d,J=6.9 Hz 2H), 2.90 (m, 1H), 2.59 (m, 1H), 2.35 (s, 6H), 1.84 (m, 2H), 1.78 - 1.63 (m, 2H), 1.44 (s, 911), 1.29 (m, 3H) (methanol-dy) 9.20 (s, 1H), 8.65 (s, 1H), 8.30 (m, 2H), 8.21 - 7.96 (m, 4H), 7.53 (d, J \ . 737 - | =8.4 Hz, 21), 7.35 (dd, / = 8.5, 6.5 lz, 37C E (M+HD) 151-133 LHD, 7.28 (d, J = 7.5 Hz, 2H), 4.44 (5, 2H), 3.91 -3.40 (m, 9H), 2.38 (s, 6H), 1.50 (s, 9h } (methanol-dy) 9.18 (s, 1H), 8.61 (s, 1H), 8.31 (m, 2H), 8.14 (m, 2H), 8.06 (d, J = 9.0 . : 725 ne 19 Iz, 210), 7.53 (d, J = 8.5 Hz, 211), 7.32 (dt, J :
BC E oat) | PT 2960,7.0 He, 3H), 4.02 (5. 2H). 3.38 - 3.34 (m, 2H), 3.22 - 3.03 (m, 2H), 2.37 (s, 611), 1.74 (m, 2H), 1.45 (s, 9H) : (methanol-dy) 9.18 (s, 1H), 8.62 (s, LH), 8.38 = 7.97 (m, 611), 7.51 (d, J=8.4 Hz, : \ , 755 210), 7.32 (dd, J = 8.5, 6.6 Hz, LH), 7.25 (d.
C ' . 140 [] 4 ’ 3 3 :
IC E Met) | TIE 6 HL 281), 4.40 Gs, TH), 4.06 (mr, 2H). 3.91 -3.74 (m, 21), 3.56 - 3.41 (m, {I), : 2.36 (s, 6H), 1.44 (s, 91D) :
Synthesis . 0 I N! iD Method MS mp (°C) LI NMR (8) (methanol-d,) 9.16 (s, LH), 8.58 (s, 1H), : 8.28 (d, J =7.4 Hz, 2H), 8.16-7.76 (m, 4H), . 755 Ap 1c 7.52 (p, J = 8.8 Hg, 211), 6.83 (1m, 211), 4.04 60C E at | POY 280 Ha 28), 3.90-3.73 (m, 3H), 3.55- 3.37 (m, 2H), 3.14-2.75 (m, 311), 2.30 (s, 610), 1.99-1.80 (m, 2H), L.43-1.31 (m, 2k) (methanol-dy) 9.12 (s, 1H), 8.12 = 8.07 (in, 2[0), 8.02 — 7.96 (m, 2h), 7.55 - 7.50 (m, 2M), 7.50 = 7.45 (m, 21D. 7.43 (d, J =7.7 7 C 61C KE Nn 7 Hz, 1H), 7.31 (d, J = 7.6 Hz, 2H), 4.03 (s, 2M), 3.25 (dt, J = 15.5, 7.0 Hz, 411), 2.84 (5s, 3), 2.04 (s, 615), 1.81 — 1.66 (m, 2{1), 1.44 (s, 9H) (methanol-d,) 8 9.18 (s, 11), 8.56 (m, LID), 8.26 (m, 2H), 8.16 — 7.84 (m. 4H), 7.52 (m, 665 2H). 7.27 (m, 1H), 7.22 (m, 2H), 4.00 (s. 62C K (M+) 110-120 | 211), 3.28 (m, 311), 3.06 — 2.83 (m, LID), 2.75 (t, J =12.2 Hz, 1H), 2.34 (s, 6H), 2.21 — 1.83 (m, 4H), 1.72 (m, 1H), 1.47 — 1.19 (m, 21D (methanol-dy) 9.18 (s, 1H), 8.63 (s, 1H), 8.28 (m, 2H), 8.13 = 7.97 (m, 4H), 7.51 (d, J nr 655 c = 8.3 Hz, 21D, 7.31 (dd, J = 8.3, 6.5 Hz, 63C K Mary | 280 iy 794 (4, 7 = 7.6 He, 2H), 4.32 — 4.07 (m, 3H), 3.98 — 3.81 (m, LH), 3.72 (s, 1H), 2.35 (s, 611) {(methanol-d,) 9.19 (s, LH), 8.58 (s, 1H), 655 8.28 (m, 2H), 8.14 - 7.97 (m, 4H), 7.51 (m, 64C K (M+) 83-112 | 21D), 6.78 (s, 2H), 4.00 (m, 211), 3.81 (s, 3H), 3.10 — 2.93 (m, 4H), 2.30 (s, 6H), 1.91 (m, 217) (methanol-dy) 9.20 (s, 110), 8.65 Gs, LI), 667 8.27 (m 2H). 8.11 ~ 7.99 (m, 4H), 7.52 (d, J 65C K (MIT) 128 dec | = 8.3 Hz, 2H), 6.78 (s, 210), 4.40 (s, 2H), 3.87 {m, 4t1), 3.53 (s, 3H), 2.32 (s, 611), : 1.33 (m, 4H) : (methanol-dy) 9.20 (s, 111), 8.56 (s, 111), 625 8.27 (m, 2H), 8.12 = 7.99 (m, 3H), 7.53 (d, J : 66C K (M+H) 100-105 | = 8.4 Hy, 2H), 7.24 (m, 4H), 3.99 (s, 2H), 3.42 (m, 2H), 3.05 (m, 211), 2.36 (s, 611), : 1.99 — 1.88 (m, 2H)
Synthesis . o i 1 (methanol-dy) 9.20 (s, 1H), 8.74 (s, LH), 8.33 —8.25 (m, 2H), 8.12 — 7.98 (m, 41D), 67C K 636 237-240 | 7.53 (d, J = 8.3 Hz, 211), 7.33 (dd, J = 8.5, (M+H) dec 6.4 Hz, 1H), 7.26 (d, J = 7.5 Hz, 2H). 4.55 (s, 211), 3.92 (m, 411), 3.37 (m, 2H), 3.31 (m, 21D), 2.38 (s, 6H) (CDC) 8.56 (s, LH), 8.33 (s, 1H), 8.22 (d, J . 581 = 8.1 Hz, 210), 7.90 — 7.70 (m, 411), 7.39 (d, eC I Main | B80 CR 710 21h, 6.72 (5, 210), 4.01 (5. 21D), 3.87 = 3.73 (s, 3H), 2.18 (s, 6H) (CDC3) 8.65 (s, LH), 8.31 (s, 1H), 8.23 (d, J 70C 592 (M+) | 134-138 | = 8.3 Llz, 211), 7.83 (m, 4k), 7.50 (d, J = 8.1
Hz, 2H), 7.45 — 7.38 (m, 3H), 4.05 (s, 2H) (CDCly) 8.62 (s, 111), 8.32 (s, 11D), 8.23 (d, J ssi =8.3 liz, 211), 7.88 = 7.74 (m, 411), 7.40 (d, 71C F (Ms mn 104-111 | J=8.3 Hz, 2H), 7.34 — 7.26 (m, 1H), 7.20 : (d, J =17.5 Hz, 211), 4.02 (s, 211), 2.22 (s. 611) (CDCl3) 8.58 (s, 1H), 8.33 (s, 1H). 8.23 (d, J = - 21 ¢ ’ 4 = 3.. nC o 565 (18-121 | = 83 Hz 2H), 7.81 (m, 4H), 7.40 (d, J = 8.3 (M+H) Hz, 2H), 7.01 (d, J = 0.4 Hz, 2H), 4.01 (s, 2H). 2.34 (s, 3H), 2.17 (s, 6H) (CDCL3) 8.58 (s, 111), 8.30 (s, 1H), 8.23 (d, J =8.3 He, LH), 7.81 (m, 2H), 7.49 (d, J =4.0 - 565 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.34 (s, 73C F (M+) 145-150 10), 7.18 (d, J = 7.8 Hz, LID), 4.01 (d, J = 1.4 Hz, 111), 2.83 (heptet, J = 6.8 12, 1H), 1.23 (1, J = 6.6 Hz, 3H). (methanol-dy) 9.20 (s, 111). 8.38 (s, LI), 8.31 - 8.24 (m, 2H), 8.08 — 8.00 (m, 2), 682 7.95 — 7.88 (m, 2H), 7.55 — 7.48 (m, 3H), 74C - 4c G oan | P0193 748 2736 (m, Si). 7.31 (d, J = 7.7 Hz, 2H), 3.60 (q, J = 7.2 Hz, 4H), 2.20 (s, 6H), : 1.07 (, J =7.2 Hz, 6H); (CDCl) 8.56 (s, 111), 8.23 (s, 111), 8.19 (d, J . = 8.4 Hz, 2H), 7.84-7.73 (m, 5H), 7.41-7.33 75C , >C G 617 (M+) (m, 3H), 7.21 (d, J =7.2 Hz, 2H), 7.16 (s,
ITD), 7.12 (d, J = 3.2 Lz, 1H), 2.20 (s, 611). :
Synthesis . 0 ] (CDCI3) 8.56 (s, 1H), 8.25 (s, 1H), 8.20 (d, J \ = 8.4 Hz, 2H), 7.80 (dd, J =8.7, 5.6 Hz, 76C G THM) ALL), 7.48-7.34 (m, 811), 7.26 (d. J = 7.7 Hz, 21D), 7.08 (s, 1H), 2.20 (s, 61) (methanol-dy) 9.14 (s, LH), 8.21 ~ 8.13 (m, 655 3D, 8.06 = 7.99 (m, 2I1), 7.86 ~ 7.75 (m, 77C G MF) 261-263 | 4H), 7.50 (Jd, J =8.3 Hz, 2H), 7.28 - 7.18 (m, 31D, 7.14 (d, J=7.9 17, 21D), 6.72 (s, 11D), 0.09 —-0.09 (m, 611) (CDC13) 8.55 (s, 1H), 8.22 (s, 1H), 8.18 (4, J 78C G 694 = 8.3 Hz, 2H), 7.79 (dd, J = 8.7, 5.1 tz, ; ’ ! (M+10) 411), 7.37 (d, J = 9.0 Hz, 211), 7.23-6.94 (im,
TH), 6.26 (s, 1H), 2.17 (s, 6H) (CDCI3) 8.55 (5, 1TH), 8.23 (s, 111), 8.19(d, J 678 =8.3 lz, 2H). 7.79 (d, J = 8.7 lz, 411), 7.43 79C G (M+) (d, J = 8.3 He, 2H), 7.37 (d, J = 8.9 He, 2H), : 7.23-7.16 (m, 30), 7.08 (d, J = 7.4 Hz, 2H), 6.35 (s, 1H), 2.18 (s, 6L1) (methanol-d;) 9.23 (s, 1H), 8.40 (s, 1H), 600 8.26 (m, 20), 8.22 (s, IIT), 8.07 — 8.00 (m, 80C G (M+H) 215-219 | 3H), 7.91 (d, J =8.4 Hz, 2H), 7.51 (d, J = 8.3 Hz, 2H), 6.90 (s, 1H). 3.88 (s, 3H), 2.13 (s, 611) (CDCl3) 9.42 (s, LI), 8.59 (s, 1H), 8.28 (d, J : 551 = 8.4 Hz, 2H), 8.01 (d, J = 8.3 Hz, 2H), 7.80) 81C I (M11) 200-213 | = 7.77 (m, 2H), 7.43 7.34 (m, 2), 7.07 (d,
J=7.5Hz 2H), 6.98 (dd, J=8.2, 6.7 Hz, i
LH), 3.90 (s, 2H), 2.17 (s, 6H) (CDCI3) 9.46 (s, 11D), 8.60 (s, 11D), 8.29 (d, J 565 = 8.4 Hz, 2H), 8.02 (d, J = 8.4 Hz, 2H), 7.89 : 82C I (M11) 225-232 | =7.76 (m, 2H), 7.40 (d, J = 8.3 Hz, 2H), 6.88 (s, 211), 3.90 (s, 21D), 2.28 (s, 31D), 2.13 : (s, 6H). : (CDCl3) 9.44 (s, 1H), 8.60 (s, 1H), 8.30 (d, J 531 = 8.4 Iz, 2I0), 8.02 (d, J = 8.4 Hz, 211), 7.82 ; 83C I (M+) 211-215 {(d,J=9.1 Hz, 2H), 7.40 (d, J = 8.3 Hg, 2H). : 6.63 (s, 2H), 3.90 (s, 2H), 3.78 (s, 311), 2.15 ! (s, 61D
Synthesis \ Oye | { : (CDCl3) 9.42 (s, 1H), 8.40 (s, 1H), 8.18 (d, J = 8.24 Hz, 211), 8.07 (d, J = 8.28 Hy, 2), ( 2 . 84 PIE 250 dee |g gg (4, J = 8.24 Hy, 200), 7.76 (d. J = 8.28
Hz, 2H), 7.64-7.58 (m, 3H), 4.42 (s. 2H) (CDC) 89.36 (s, 1H), 8.60 (s, 1H), 8.30 : (d, J = 8.4 11z 2H), 8.01 (d, J = 8.4 liz, 211), 7.86 — 7.77 (m, 2H), 7.40 (d, J = 8.3 Ho, : 85C [ tn | 146-149 | 210,732 (dd, J = 69,2317, 111), 7.24 - 7.12 (m, 2H), 6.91 (dd, J = 7.1, 2.0 tz, 111), 3.93 (s, 2H), 3.15 — 2.97 (im, 1H), 1.21 (d, J = 6.9 Hz, 611) (CDCl) 3 8.81 (bs, LH), 8.57 (s, 111), 8.20 (d, J =8.3 Hz, 2H), 7.87 — 7.75 (m, 4H), 7.39 (d, J = 8.3 Iz, 211), 7.32 — 7.25 (m, : 566 LH), 7.10 (2dt, J = 7.4, 1.5 Hz, 2H), 6.83 (d, 86C i vier | 163109 6s Hy 1H). 3.96 (1 J = 6.1 Hz, 2H), 3.13 (heptet, J = 6.9 Hz, 1H), 2.99 — 2.88 (m, 2H), 2.49 = 2.36 (m, 2H), 1.29 = 1.21 (m, 6H). (CDCly) 8 8.81 (s, 1H), 8.66 (s, 1H), 8.21 (d, J = 8.3 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 7.81 (t, J = 10.2 Hz, 4H), 7.30 = 7.26 (m, 550 211), 7.17 = 7.04 (m, 1H), 6.83 (d, J = 6.4 Co 87c J ein | B79 1 IH), 3.96 (LT = 6.1 Hz, 2H), 3.13 (heptet, J = 6.9 Hz, LH), 2.97 - 2.90 (m, : 201), 2.47 2.38 (m, 2H), 1.25 (d, J =7.5
Hz, 6H). : (CDC) § 8.58 (s, 1H), 8.30 (s, 1H), 8.22 : (d, J = 8.3 Hz, 211), 7.82 (dd, J = 8.7, 72
Hz, 4H), 7.48 (dd, J = 4.1, 1.3 Hz, 2H), 7.40 579.2 (d, J =8.3 Hz, 211), 7.37 — 7.30 (m, 151),
C H 8-182 . : 88C F etn | 78820907 (my 1H), 4.23 (dg, J = 14.5, 7.2 Ho, 1H), 2.83 (dd, J = 14.6, 6.9 Hz, 1H), 1.79 (d, J =17.2117, 3H), 1.22 (ddd, J = 12.1, 6.9, 1.9 Hz, 611). (CDCl3) 8 8.58 (s, 1H), 8.32 (s, 1H), 8.23 550 (d, J = 8.4 17, 2H), 7.90 = 7.75 (m, 411), 89C I (Mary | 205-206 | 7.52744 (m, LID, 7.40 (d, J =8.3 Hz, 2H), 7.10 (dd, J = 8.6, 7.4 Hz, 2H), 4.04 (s, 3 200).
Synthesis \ ° | onl
ID Method MS mp (°C) LI NMR (§) (CDCl13) 8 8.58 (s, 1H), 8.31 (s, LH), 8.23 566 (d, J=8.3 Hz, 2H), 7.82 (1, J = 8.5 Hz, 4H), 90C Ir (M+11) 148-151 | 7.46 — 7.31 (m, 3H), 7.25 - 7.18 (m, 21D), 4.02 (s, 2D), 2.53 (4, J = 7.6 Hz, 21), 2.21 (s, 3H), 1.26 — 1.16 (m, 3H). (CDCl3) 8 8.58 (s, LID), 8.36 (s, 111),8.23 (d, J =R8.3 Hz, 2H), 7.88 — 7.76 (im, 4H), 4%) — | =8.5 2.5 91C 554 177.235 7:49 7.35 (m, 31D), 7.01 (dd, J ) 8.5.25 (M+11) Hz, LID), 6.96 (dd, J =7.8, 1.0 Liz, LID), 6.91 (t, J=2.2 Hz, 1H). 3.98 (s, 2H), 3.85 (s, 31D). (CDCl) d 8.58 (s, 1H, 8.32 (s, 11D), 8.22 (d, J=8.4 Hz, 2H), 7.86 — 7.77 (m, 4H), < . 554 o | 7.50 ~7.43 (m, LH), 7.40 (d, J =8.3 liz, 2 oH - 92C : Mat | O08 or 799 707 (mm, LH), 7.14 — 7.04 (m, 2H). 4.01 (d, J=17.2Hz, IH), 394d, J= 17.3 117, 111), 3.84 (s, 311). (CDCl3) 6 8.58 (s, 1H), 8.31 (s, 11), 8.27 - 579 8.18 (m, 2H), 7.88 — 7.77 (m, 4H), 7.43 — 93C F M11) 183-186 | 7.37 (m, 3), 7.34 (t, J = 7.8 Hz, 1H), 7.30 —7.26 (m, 1H), 4.07 (d, J= 17.4 Hz, 1H), 4.00, J=17.4 Hz, 1H), 2.29 (s, 3H). (CDCI5) 8 8.58 (s, 11), 8.31 (s, 1H), 8.23 552 (d, J =8.4 Hz, 2H), 7.86 — 7.78 (1m, 4H), 94C F (M+) 134-136 | 7.49 - 7.32 (m, SH), 7.24 — 7.18 (m, 1H), 4.06 -3.94 (m, 2I0), 2.56 (q, J =7.6 117, 2H), 1.26 — 1.18 (im, 3H). (CDC13) 68.59 (d, J =4.8 Hz, 1H), 8.26 (m, 05(" 576.1 195-201 310), 7.89 — 7.74 (m, 4D), 7.52 -7.31 (m, (M+H) 4H), 7.24 — 7.13 (m, 1H), 4.05 (d, J =0.9
Hz, 211). (300 Milz, CDCIl3) 8 8.58 (s, 111), 8.33, J 600 ' =7.9 Hz, 1H), 8.24 (s, 1H), 8.21 (s, LH), 96C F (MH) 182-185 | 7.86 ~ 7.76 (m, 4H), 7.53 (t, J = 5.9 Hz, 310), 7.44 — 7.29 (mm, 811), 3.80 = 3.73 (m, 1H), 3.59 = 3.51 (m, 1H).
Synthesis , op (CDCl) § 8.57 (s. LH), 8.37 (s. LH), 8.23 ser (d, J = 8.4 Hz, 2H), 7.89 — 7.73 (mn, 4H), 97¢ I Opp | 234236 | 7457.29 (m, 311), 6.79 (dd, J =82,2.2
Hz, LH), 6.70 (d. LD), 6.57 (s, LF), 3.96 (s. 2H), 2.98 (s, 611) (CDCl) § 8.55 (s, 111), 8.29 (s, 1H), 8.21
I (d, J = 8.4 Hz, 2H), 7.86 — 7.71 (m, 4H), 98C F win | 225226 | 742-723 (m, 310), 6.63 (d, J =8.5 Hy, (M+ 201), 4.07 (q, J = 7.0 Lz, 411), 3.94 (s, 241), 131 (1, J = 7.0 Hy, 6H) (CDCl) 3 8.58 (5, 1H), 8.32 (s, 11), 8.23 voc 679 (M- | 3 ns) | (0h = 8:4 He. 210, 7.89 7.77 (an, 41),
H) 7.70 (d, J = 8.1 Hz, 2H), 7.40 (d. J = 8.3 Hy, 2H), 7.29 — 7.20 (m, TD), 4.04 (s, 21D) (CDCl) 5 8,58 (s. LID), 8.30 (s, 111), 8.22 ‘on (d, J = 8.4 Hz, 2H), 7.93 — 7.70 (m. 4FD), 100C r arn | 118120 17.39, J =9.0 Fiz, 26D), 78 (¢, 11D), 7.19 (d, J = 7.7 Hz, 21), 4.01 (s, 2H), 2.21 (s, 6H). (CDCl3) 8 8.60 (s, 1H), 8.32 (s, LH), 8.23 553 (d. J = 8.4 Hz, 2H), 7.89 — 7.74 (m, 4H), 101C F ary | 106-107 | 7.39 (4, 7 =8.3 Fy, 2H), 6.56 (5, 1H), 4.01 (5, 2H), 3.94 (s, 311), 2.32 (s, 311), 2.16 (s, 3H) 539 (M- (CDCl) § 8.27 (s, 1H), 7.95 = 7.71 (m, SH), 102C F oS 123-126 | 7.60 (d, J = 1.3 Hz, 1H), 7.53 — 7.43 (m, 411). 7.45 7.32 (m, 311), 4.04 (s, 211) (CDCl3) § 8.28 (5, 1H), 7.93 (dd, J = 5.4, 4.1 . ! 551 roe | Hz, 31D, 7.78 (m. 411), 7.36 — 7.23 (m, 311), 103¢ t MH) | P90 0 (0 = 7.6 Ha, 2H), 6.81 (d, J = 2.5 Ho. ;
THD, 4.00 (s, 2H), 2.21 (s, 6H) (CDCl) 68.27 (5, 111), 8.16 (5, 1H), 8.03 Gs, os LED), 7.80 = 7.71 (m, 4H), 7.57 (d. J = 8.3 104C F ovary | 100-102 | Fz, 2H), 7.30 (dd, J = 28.7, 5.8 Hy, 3H), : 7.19 (d, J = 7.6 117, 211), 401 (s, 211), 2.21 : (s. 6H) :
Synthesis , o | onl
ID Method MS mp (°C) IENMR (3) (CDCLy) 8 8.58 (s. LH), 8.31 (s. LH), 8.23 = 17 7} 9 1) 050 586 200211 | @ 4 =7:8 Ha, 2H), 7.82 (m, 4H), 7.39 (d. J (M+11) =8.0 Hz, 211), 7.19 (s, 211), 4.01 (s, 210), : 2.10 (s, 6H) : (CDC3) § 8.58 (s, 111), 8.30 (s, 111), 8.22 : ss (d. J =8.2 Hz, 2H), 7.81 (m, 411), 7.58 (dd, 106C F (Marry | 180-182 | J=60,3.3 Hy, 1H), 7.43 (ddd, = 23.4, 11.3, 5.5 Hz, SH), 4.02 (dd, J = 29.0, 17.4
Hz, 2D (CDCl) 8 8.58 (s, 1H). 8.32 (s, 1H), 8.22 s06 (dd, J = 10.0, 8.6 Hz, 411), 7.82 (m, 411), 107C (M+H) 227-232 | 7.49 (d, J = 8.5 112, 2), 7.40 (d. J = 8.6 Liz, 2H), 4.42 (4, J = 7.1 Hz, 2H), 4.00 (s, 2H), ;
La! (t, J=7.1 Hz, 31D (CDCl) 3 8.58 (s. 111), 8.28 (d, J = 15.0 112,
IH), 8.23 (d, J = 8.3 Hz, 2H), 7.87 = 7.76 50 (m, 4H), 7.53 — 7.30 (m, 511), 7.18 (ddd, J =
OSC F (aby | H67L7L | 78,42 121, 1H), 403 - 3.98 (m, 2H), ; 2.53 (dd, J=14.1,7.0 Hz, 1H), 1.77 — 1.56 ; (m, 210), 1.26 = 1.16 (m, 311), 0.78 (td, J = 7.4,2.3 Hz, 3H). : (CDCl3) 6 8.25 (5, 1H), 7.73 (d, J = 7.4 Hy, cso 411), 7.55 — 7.43 (m, 211), 7.43 — 7.36 (m, ; 109C F Moty | 105-111 | TH), 7.10 (tJ = 11.6 Hz, 4H), 4.90 - 4.79 (m, 1H). 4.04 (s, 2H). 3.76 (s, 3H), 3.73 — 3.62 (m, 111), 3.52 — 3.35 (m, IH) (CDCly) 8 8.25 (s. LH), 7.82 — 7.64 (m, 410), 611 7.30 (t, 1H), 7.22 - 6.99 (m, 6H), 4.83 (dd, J
LOC r (Mal) = 12.8, 6.5 Hz, 1H), 4.00 (s, 2H), 3.89 — 3.59 (im, 4H), 3.44 (dd, J = 17.2, 6.5 Hz, ; [H), 2.20 (s, 611). (CDCly) 5 8.58 (s, LT), 8.30 (s, 111), 8.23 ; (d, /J=8.4 Hz, 2H), 7.86 — 7.77 (m. 4H), : 580 7.39 (4, J = 7.8 Hz, 3H), 7.34 — 7.27 (m
Hic F 209-2 ;
MD) | 209210 00,700 d= 7.4 112, 111), 4.03 5. 24D), ] 2.86 2.71 (m, 1H), 2.21 (s, 3H), 1.21 (2d,
J =6.7 Hz, 6).
Synthesis . Ope | ] (CDCLy) § 8.58 (s. LH), 8.32 (s, LH), 8.23 (d, J =8.4 Hz, 2H), 7.87 — 7.75 (m, 4H), . . 564 7.43 -7.33 (m, 41D), 7.26 — 7.19 (m, 211), ; 2 3 - - i
H2C t oat) | PHS 40 (s,200), 1.86 - 1.77 (m. LHD), 0.90 — 0.83 (m, 21), 0.77 - 0.68 (m, | FD, 0.67 — ; 0.59 (im, LHD. (Acetone-Dg) § 9.20 (s, 1H), 8.28 (d, J = 8.2 si | LLt1e. | 117310, 8.13 (d, J=9.0 Hz, 211), 7.94 d, J 1130 Nt) ba | = 8:2 112, 210), 7.60 (d, J = 8.3 Liz, 211), 7.39 == (T= 17.1 Hy, 4H), 4.15 (q, J = 17.3 Hy, 211). 2.23 (s, 3H) (CDCl) 5 8.58 (s, L11), 8.33 (s, LH), 8.22 sc (d, J=8.3 Hz, 2H), 7.88 — 7.67 (m, 4H), 114C rm ary | 203-205 | 738(d, J = 8.4117, 210), 7.14 (d, J =83 117,
LH), 6.87 (d, J = 8.9 Hz, 2H). 3.98 (s. 2H). 3.83 (s, 3H), 2.20 (s, 3H) (CDCI) 3 8.58 (s, 111), 8.35 (s, 111), 8.23 . . 554 | oo ae, | (47 =8.2 Hz, 24), 7.82 (m, 4H), 7.40 (d, J 11 E MH) | 20120% | Je Hy 2H), 7.30 (d, 2H), 7.03 (d. J = 8.8 :
Hz, 2H), 3.97 (s, 2H), 3.86 (5, 311) (CDCL,) 5 8.58 (s. 1H), 8.31 (s, 1H), 8.22 (d, J =8.3 Hz, 2H), 7.88 — 7.72 (m. 4H), 48 - 7.32 . -7.2
Lc . 568 02.97 | 7487.32 (m. 310,7.31 7.20 (m, 11D), (M+11) 7.13 — 6.97 (m, 2H), 4.09 (q, J = 7.0 Hz, 2H), 3.95 (J = 11.7 Hz, 2H), 1.33 (1, J = 7.0 Hz, 310). (CDCly) 8 8.59 (s, 111), 8.54 (dd, J=4.8. 1.3 : 530 Hz, LHD), 8.28 (s, 1H), 8.22 (d, J = 8.4 Hz,
L17C F ain | 127-132 [21D,784-7.77 (m, 411), 7.77 =7.72 n, 1H). 7.38 (dd, J = 7.7. 5.0 Hz. 3H), 4.02 (d.
J =12Hz, 2H), 2.30 (s, 3IT) (CDC) 8 8.67 (s. 111), 8.59 (s, 111), 8.24 539 ops | J =84 Hz 2H), 7.99 (d, J = 8.4 He, 1H), 118C F oth | deny | 7:84 (dd J =8.3, 38 Ho, 41D), 7.80 Gs, LT), 7.42 —7.39 (m, 311), 4.03 (d, J = 1.3 Hz, : 2H), 2.26 (s, 3H). 136 i
Synthesis \ 0 } 1 : (CDCLy) 6 8.58 (5. LH), 8.29 (s. LH), 8.23 (d, J = 8.4 Hz, 2H), 7.88 — 7.77 (im, 4H), . 580 aia | 748 27.34 (m, 5H), 7.23 = 7.18 (m, 11D),
HOC ony | P38 406 23.03 (m, 28D), 2.40 (qd, J = 14.2, 7.3
Hz, 2H), 1.94 — 1.81 (m, 111), 0.89 (d, J = : 6.6 Hz, 611). (CDC) 8 8.67 (5, TH), 8.30 (s, 1H), 8.24 : <10.7 (d, J =8.3 17, 210), 7.92 (d, J = 8.5 117, 210), 120C L Map | 153159 | 7.82 (m, 310, 4.01 (d. J = LS Hz, 211), 3.80 3.64 (m, 2H), 2.91 = 2.76 (m, 2H), 1.30 —
I.t4 (m, 611) (CDCl) 8 8.57 (d, J = 7.4 Lz, LL), 8.30 (s. ao | THD, 8.23 (d, J = 8.4 Hz, 2H), 7.87 — 7.78 121C F th ah (m, 411), 7.49 — 7.33 (m, 511), 7.29 — 7.26
CT (my, LHD, 6.03 (s, LHD, 3.95 (s, 21D), 1.84 (d,
J=13 Hz, 3H), 1.71 (d, J = 1.2 Hy, 3H). (CDCly) 8 8.58 (s, 1H), 8.24 — 8.18 (m, 21D), 7.99-7.94 (m, 2I1), 7.84 — 7.78 (m, 2H), 7.47 (dd, J = 5.0, 1.1 Hz, 2H),7.40 (d, J = 21 - - i 5793 | go 7; | 83 Hz 2H), 7.34 (ddd, /=79, 5.1, 3.7 Hz, (M+1) 1H), 7.18 (d, J = 7.6 Hz, 1H), 4.00 (d, J = 1.5 Hz, 2H), 3.72 (dd, J = 7.0, 5.1Hz, 2H), 2.94 - 2.80 (m, LI), 2.22 (s, 31D, 1.23 (im, 9H). (CDCl3) 6 8.62 (s, 1H), 8.54 (d, J = 3.2 Hz, . 553 ac | 11D). 8.28 = 8.19 (m, 31), 7.82 (d, J = 8.8 2 4 - : 123¢ : +t) | BOI pg sk), 7.43 © 7.37 (m. 3H, 4.02 (5. 2H). 2.63 (d, J = 7.6 Hz, 2H), 1.22 (s, 3H) (CDCl3) § 8.58 (s, 111), 8.29 (s, 111), 8.23 608 (d, J = 8.4 Hz, 2H), 7.89 — 7.75 (in, 4H), : 124C F (Many | 140-145 | 7.58 = 7.51 (m, 1H), 7.49 7.36 (m, SH), ) 4.04 (d, J = 17.4112, L11),3.97 (d, J = 17.4
Hz, LH). (CDCl3) 3 8.58 (s, LH), 8.31 (s, 1H), 8.22 : (d, J=8.4 lz, 21), 7.86 — 7.78 (m, 4D), g ] 580 7.65 (Ud, J = 8.1, 1.4 Hz, 1H). 7.49 — 7.42 125C F - ’ ’ ]
Many | 300 Tn, 7.40 (0 = 8.3 11, 210. 7.35 (dt, =7.6,1.5 Hz, 1H), 7.05 (dd, J = 7.8, 1.5 Hz,
LH), 3.95 (s, 2H), 1.38 (s, 9H).
: Synthesis o | ! (CDCly) 6 8.58 (s, LH), 8.29 (s, 1H), 8.23 : 500 (d, J = 8.4 Fz, 2H), 7.87 - 7.77 (m, 4H), 126C watny | 75-177 | 7:52(ddd. J =8.1,6.0, 34 11z, LD), 7.44 - ( 7.34 (mn, SH), 6.46 (1, Jur = 73.5 Hz, LD), 4.05 = 3.95 (m, 2H). (CDCL3) 3 8.58 (s, 111), 8.32 (s, 111), 8.22 (d, J = 8.3 Hz, 2H), 7.87 = 7.75 (mm, 4H),
S _ 2 / M16 — T IA 2 b 176 578 Hers | 743732 (m, 41D. 7.26 - 7.24 (m, 20), (M+I1) 4.23 (q. J = 7.3 Hz, LI), 1.85 — 1.78 (m, 4H), 0.90 — 0.78 (m, 2FD), 0.78 — 0.69 (mn,
LTD), 0.65 — 0.55 (m, IH). (CDCly) 8 8.58 (s. LH), 8.29 (d, J = 7.8 Fz, 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.88 — 7.74 . } 580 (m, 410), 7.48 — 7.30 (m, 511), 7.20 (t, J = ; nD 1 - B 128C I +k) | TU EL Lh), 4.26 — 4.14 (om, LE), 2.50 2.46 (m, 2H). 1.79 (d, J =7.3 Hz, 3H), 1.69 : ~ 1.56 (nm, 211), 0.93 (t, J = 7.3 117, 311). (CDCL3) 8 8.58 (s, LH), 8.30 (s, 111), 8.22
C06 (d, J = 8.4 Hz, 2H), 7.87 — 7.76 (m, 4H), 129C F (Matn | 140-142 | 7.53 -7.47 (m, 210), 7.44 - 7.35 (m, 310), 4.27 (q, J = 7.3 Hz, 1H), 1.82 (d, J =7.3 Hz, 3H). (CDCl) § 8.58 (s, 111), 8.31 (s, 111), 8.22 “RAM, N _ : ) : 590 93.97; | (J = 8.4 Hu 2H). 7.88 ~ 7.76 (m. 4H), 130C F HD | 191-104 | 7:48 = 7:34 (m, 4D, 720 (1, J = 12.4, 6.1
Hz, LF), 4.35 — 4.18 (m, LID), 1.81 (2d, J = 7.3 Hu, 3H). (CDCl) 8 8.58 (s, 1H), 8.32 (s, 1H), 8.26 — 8.20 (m, 2H), 7.86 — 7.78 (m, 411), 7.53 — : 572 - 08: ; 131C F TM RS 7.42 (m, 1H), 7.40 (d, J = 8.3 Hz, 2H), 7.09 :
CURR, J =8.1 Hz, 2H), 4.26 (g, J = 7.3 Hz, 11D), 1.80 (d, J = 7.3 117, 311). ] (CDCl3) 6 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, J = 8.4 Hz, 2H), 7.80 (ddd, J = 9.5, 6.9, 4.9 iz, 411), 7.43 — 7.33 (m, 411), 7.31 — 1320 552 103.196 | 7-21 (0, 2H). 4.05 (id, J =9.4, 7.1 Hz, LH), : (M+1D) 3.97 = 3.87 (m, LI), 3.42 = 3.33 (m, IT), : 3.33 -3.24 (m, LI), 3.12 (heptet, J = 6.8
Hz, 1H), 1.27 (d, J = 6.8 Hz. 3H), 1.22 (d, J 1 =6.9 117, 3H).
(CDCI) 88.55 (d, J ="7.1 Hz, 1H), 8.23 (s, 538 {HD, 8.17 (d, J =8.4 Hz, 2H), 7.80 (dt, J = 133C J (MH) 167-169 | 11.4, 6.2 Hz, 411), 7.43 — 7.23 (in, 611), 4.00 (s. 2H), 3.32 (s, 2H). 2.67 (4, J = 7.6 Hz, 2H), 1.25 (dd, J = 9.6, 5.5 Hz, 311). (CDCI) 8 8.65 (s, HI, 8.22 (s, 11), 8.18 (d, J = 8.4 Hz, 2H), 7.94 — 7.88 (m, 2H), 7.81- 7.78 (m, 41), 7.41 (dd, J=7.8, L.5 oo 536 217-220: Hz, 11D, 7.39 - 7.33 (m, 111), 7.30 -7.24 134C J a | (m, THD), 7.23 (dd, J =7.8, 1.5 Hz, 1H), 4.09 (M+) 230-232 oa } ~4.02(m, 11), 3.98 - 3.883 (m, 111), 3.43 - 3.24 (m, 2H), 3.12 (heptet, J = 6.9 Hz, LL), 1.27 (d, J = 6.8 Hz, 3H), 1.22 (d, J = 6.9 Hy, 3H). (CDC) 88.56 (s, LH), 8.19 (dd, J = 12.7, 9.0 Hz, 3H), 7.84 — 7.74 (mm, 4H), 7.37 (dd, J 566 = 14.9, 6.1 iz, 411), 7.26 (s, 111), 7.21 (d, J 135C J (MH) 167-169 | =7.6 Hz, 1H), 4.17 — 3.85 (m, 2H), 3.42 - 322 (m, 2H), 2.82 d, J =23.6 Hz, 1H), 1.80 — 1.55 (m, 21D), 1.23 (2d, J = 6.9 Hz, 3H), 0.82 (21, J =7.4 Hz, 3H). (CDCI3) 8 8.56 (s, 1H), 8.22 (5, 1H), 8.17 (d, J =8.41lz, 211), 7.84 — 7.74 (m, 41), 557 7.39 (d,J=8.3 Hz, 2H), 7.24 (d, J =17.5 Hz, 136C J MATT) 143-147 | 1H), 7.19, J=6.4 Hz, 1H), 7.15(, J = 7.3 Hz, 11),3.92 (qt, J = 10.1, 7.3 lz, 2H), 3.43 - 3.28 (m, 2H), 2.72 - 2.51 (m, 2H), 2.27 (s, 3D), 1.25 (t, J = 7.6 Hz, 3). (CDCl3) 88.56 (d, J =5.3 Iz, 1H), 8.26 (s, 1H), 8.17 (d, J = 8.4 Hz, 2H), 7.84 — 7.74 554 (m, 411), 7.39 (d, J = 8.3 Hz, 2I1), 7.18 (d, J 137C J (M+I1) 183-186 = 8.5 Hz, LI), 6.81 (dt, J =8.4,2.9 Hz, 211), 3.96 (1, J =6.6 Hz, 2H), 3.81 (s, 3H), 3.30 : (t, J=6.9 Hz, 2H), 2.28 (s, 31). : (CDC) 88.56 (d, J =5.4 Hz, LH), 8.25 (s, 563 1H), 8.17 (d, J=8.4 Hz, 2H), 7.84 - 7.72 : 138C J (M411) 231-233 | (m, 411), 7.39 (d, J = 8.3 Hz, 2H), 6.67 (s, 2H), 3.92 — 3.85 (m, 2), 3.79 (s, 311), 3.34 (t, J =7.1 Hz, 2H), 2.25 (s, 6H).
Synthesis . of 1 I (CDCly) 8 8.56 (s. LH), 8.24 (s. 1H), 8.17 i. (d, J = 8.3 Hz, 2H), 7.83 — 7.73 (m, 4H), 139C J orn | 195-197 | 739d, J = 8.3 Hz, 21D), 6.95 (5, 211), 3.90 (LJ =7.1 Hz, 2H), 3.35 (1 J = 7.1 Hz, 210), 2.30 (s, 311), 2.23 (5, 610). (CDCl) 6 8.56 (s, 111), 8.24 (s, 1H), 8.17 (d, J = 8.3 Hz, 2H), 7.84 — 7.75 (m, 4H), oo 540 17.43 27.36 (m, 311), 7.30 (ddd, J = 12.6, 140C ! +n | BEI 693 Hi, 11), 7.06 - 6.97 (m, 211), 4.04 (t, J =7.0 Hz, 2H), 3.86 (s, 3H), 3.29 (1, J = 7.0 Hz, 2). (CDCl3) 3 8.56 (s, LD), 8.25 (s, LH), 8.18 524 (d, J = 8.4 Hz, 2H), 7.83 — 7.75 (m, 4H), 141C J Maly | 173-176 | 7.39, J =8.3 117, 20D), 7.34 7.23 (m, 4H), 4.01 (LJ = 6.9 Hz, 2H), 3.32 (1. / = 6.9
Hz, 2H), 2.31 (s, 3H). (CDCl) § 8.56 (5, 1H), 8.23 (5, 1113, 8.17 538 (d, J = 8.4 Hz, 2H), 7.84 — 7.74 (m, 4H), 142C J arn | 210-213 | 7.39.(d, J = 8.3 Hz, 2H), 7.22 - 7.10 (m, 3H), 3.92 (tJ = 7.1 Hz, 2H), 3.36 (1, J = 7.1
Hz, 2H), 2.28 (s, 6H). (CDCl3) § 8.56 (s, 1H), 8.23 (s, 1H), 8.18 (d, J = 8.4 117, 211), 7.83 — 7.74 (m, 411), 9 —- - 1 — 3c | 562 | ny ang | 7:38 (A.J =83 Hz, 2M), 7.30 (at, J = 74, (M+H) 4.8 Hz, 2H). 7.15 — 7.09 (m, 1H), 4.05 (ddd,
J=94,7.3,52 Hz, 1H), 4.00 3.89 (m,
LED), 3.46 — 3.30 (m. 2H). (300 MIz, CDCl3) 8 8.56 (d, J = 4.3 Hz, 11). 8.34 Gs, 111), 8.21 (s, 111), 8.18 (s, LD), 4 | 586 | 117-123; | 7.81 (dd, J = 8.9, 2.3 Hz. 4H), 7.52 (d, J = : (M+IT) | 134-138 | 6.7 Hz, 1H), 7.50 = 7.31 (m, 10H), 3.53 — 3.49 (m, 211), 2.95 — 2.90 (d, J = 6.8 Iz, 2H). (CDCl3) 3 8.56 (5. 1H), 8.26 (s, 1H), 8.18 (d, J = 8.3 Lz, 210), 7.84 — 7.74 (m, 411), 550 7.39(d, J = 8.3 Hz, 2H), 7.32 = 7.21 (in, 145C I ty | 207-209 | 31D, 7.01 (dd, J =8.9,2.5117, 111), 4.12 - 4.04 (s, 211), 3.34 (t, J = 6.9 Iz, 2H), 2.09 — 1.98 (m, 1H), 0.95 (dd. J = 8.5, 1.7 Hz, 2H), 0.72 (bs, 211).
Synthesis , 0 I 1 (CDCLy) 8 8.56 (d, J = 5.2 Hz, 1H), 8.24 (s.
LH), 8.17 (d. J = 8.3 Hz, 2H), 7.80 (dt, J = oo 554 8.2.4.6 112, 411), 7.45 — 7.36 (m, 311), 7.30 146C J Mtn | HEE 5d i TH), 7.05 — 6.95 (m, 2H), 4.13 — 4.02 (m, 411), 3.28 (t, J = 7.0 T1z, 2FD), 1.44 - 1.35 (m, 31). (CDCI) 5 8.57 (5. LH), 8.37 (s. 1H), 8.21 (d. J =8.3 iz, 210), 7.87 — 7.76 (m, 411), sso 7.40 (d, J = $4 Iz, 2H). 7.29 (dd, J = 14.2, 147C I ry | 168-170 | 60 Ha 11D, 7.24 (d, J =23 Ha, 1H), 7.09 - 7.02 (m, 111), 6.72 (dd, J = 8.0. 2.1 Hz, 111), 420 (tJ = 6.9 Iz, 211), 3.83 (d, J = 8.7 Hz. 3H), 3.24 (1, J = 6.9 Hy. 2H). (CDCly) 5 8.56 (5, 1H), 8.24 (s, 111), 8.18 (d. J =8.3 Hz, 2H), 7.80 (dt, J = 4.0.2.5 Hz,
Pp ~~ . —_ . 2 -— isc | S46 | 53006 | 4H). 7.39 (4, J =8.3 Hz, 2H, 7.30 (ddd, J (M=+11) 8.5.7.4, 4.2 Iz, 111), 7.05 ~ 6.97 (m, 210), 4.02 (tL, J = 6.9 Hz, 2H), 3.36 (1. J = 6.9 Hz, 2H), (CDCly) 3 8.56 (s, 1H), 8.18 (d, J = 2.6 Hz, 2H), 8.16 (s, 1H), 7.80 (dt, J = 8.3, 4.7 Hz, . 612 | 4H). 771 (0 J = 8.6 Hz, 20), 747 (1. T= 7.7 4 7 ND + \ 149C 7 try | 209203 11571, 7.39 (d, J = 8.3 Ha, 210). 4.18 — 4.07 (m, LH), 3.93 — 3.84 (m, 1H), 3.46 (id,
J=10.7,7.3 Hz, 1H), 3.35 — 3.25 (m, 11). (CDCl) 8 8.56 (5, 111), 8.22 (s, 111), 8.17 (d, J = 8.4 Hz, 2H), 7.80 (dL, J = 11.5. 6.2 see Hz, 4H), 7.39 (d. J = 8.3 Fz, 2H), 7.31 - 150C I an | 169-172 [727 (m, 310), 7.26 ~ 7.24 (m, LD), 4.10 - 3.89 (m, 2H). 3.38 — 3.32 (m, 2H), 2.48 (s, 211), 2.01 — 1.84 (m, 111), 0.91 (d. J = 6.2
Hz, 611). ; (CDCI) 3 8.57 (s, 1H), 8.25 (5, [H), 8.18 (d, J = 8.3 Hz, 21, 7.99 (s. 1H), 7.81 (dt, J
S64 = 8.3, 4.5 Hz, 4H), 7.39 (dd, J = 6.1, 3.5 Hz, 151C I Varn | 149-153 | 3H),7.33 7.27 (m, 2H), 6.21 (5, 1H), 3.92 (t, J=6.9 Iz, 2H), 3.26 (t, J = 6.8 Hz, 21D), 1.89 (d. J = 1 Hz, 31), 1.79 (d. J = L.1 Hz, 3H).
: . . ] (CDCl) § 8.57 (5, LH), 8.23 — 8.16 (mm, 3H), 7.83 = 7.77 (m, 4H), 7.48 (dd, J=7.5,2.0 . 576 lz, 111), 7.39 (d, J = 8.3 Lz, 211), 7.33 (dt, J 152C J +n | OI 270 20 He, 2H), 7.28 (dd, J = 9.8, 1.9 Hy,
LH), 6.52 (t, Jur = 74.1 Hz, 11), 4.06 (t, J = : 6.9 Hz, 211), 3.33 (1, J = 6.9 Llz, 2H). (CDCI) 8 8.57 (s, 1H), 8.25 (s, 1H), 8.19 504 (d, J=8.4 117,20), 7.81 (dt, J =4.1,2.6 17, {53C (V+H) 195-197 | 411), 7.58 — 7.52 (m, L11), 7.42 — 7.33 (m,
SH), 4.05 (t, J = 6.9 Hz, 2H), 3.31 (t, J =6.9
Iz, 210).
CDCl) 3 8.56 (5, 111), 8.23 (d. J = 9.8 He, 1H), 8.17 (d, J = 8.3 Hz, 2H). 7.84 — 7.74 538° (m, 411),7.39 (d, J = 8.3 17, 21), 7.35 — oo 154C J (tp | LO4167 | 7.27 (m0, 310,719 (s, LED, 3.54 -3.31 (m, : LH), 3.07 = 2.93 (m, 1H), 2.31 (d, J = 9.0
Hz, 3H), 1.62 — 1.56 (m, 111). 1.31 = 1.19 (m, 3H).
Two Isomers (CDCI) 8 8.56 (s, 2H), 8.18 : (dd, J= 10.8, 7.4 Hz, 611), 7.84 — 7.73 (m,
SH), 7.45 — 7.30 (m, 8H), 7.30 = 7.23 (m,
S66 IH), 7.20 (d, J = 6.7 Hz, 1H), 7.12 (dd, J= | + =~ 155C J Malp | 201-204 1 78,12 Hy, 111), 443 4.33 (m, LH), 4.16 (dd, J = 12.6, 6.3 Hz, 1H), 3.48 (dt, J = 13.3, 6.7 Fz, 1H). 3.37 (dd, J = 10.8, 6.2 Hz, 1H), 3.24 (dt, J = 13.7, 6.9 11z, 111), 3.08 = 2.92 (m, 3H), 1.33 — 1.16 (im, 18H). (CDC3) 68.56 (5, 1H), 8.20 (d, J = 3.4 Hz, 111), 8.16 (d, J = 8.4 lz, 211), 7.84 - 7.73
S66 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.25 — 156C J Math | 105-110 | 7.00 (m, 3H), 4.39 — 4.23 (m, 111), 3.53 3.35 (m, LL), 3.04 — 3.00 (m, 111), 2.78 — 2.49 (m, 2H), 2.28 (2s, 3H), 1.34 —- 1.08 (m, 611). : : (CDCl) 88.56 (d, J = 0.6 Hz, 1H), 821 (s, |- . So
LH), 8.17 (d, J = 8.2 Hz, 2H), 7.82 — 7.77 . 592 (m, 411), 7.49 — 7.35 (m, 411), 7.30 — 7.28 157€ ! MD | U6 (nl Lin), 4.64 — 4.57 (m, LHD, 3.44 (0d, J = 10.2, 6.3 Hz. 1H), 3.16 — 3.01 (m, 1H), 1.27 od, J=6.3 Fz, 3H).
Synthesis . 0 1 J 1 : Two Isomers (CDCl) 8 8.56 (s, 2H), 8.20 (s, 2H), 8.19 - 8.12 (im, 41), 7.84 — 7.73 (m, 8, 7.39 (d, J =8.3 lz, 41D), 7.36 - 7.29 (m, 2H), 7.25 - 7.17 (mm. 41), 4.78 - 4.55 . 572 oc ~ | (m, LH), 4.35 (dt, J=9.4,63 17, IT), 3.48 158C J oan | 201% dd, 72107, 6.5 Ha, 1H), 3.38 (dd, J = 10.7, 6.2 Hz, 1H), 3.11 (dd, J=10.7,9.4
Hz, ITD, 3.01 (dd, J = 10.7, 8.3 117, IIT), 2.35 (s, 31D, 2.30 (s, 31D), 1.26 (d, J =6.3
Hz, 3H), 1.21 (d, J = 6.4 Hz, 3H) (CDC) 88.56 (s, 111), 8.48 (dd, J = 11.9, 5.3 Hz, 3H), 7.79 (dd, J = 8.7, 6.5 Hz, 411), 607 , 7.47 (dd, J=7.8,23 Hz, IH), 742-732 s 5 an N : y 1 3 155€C J (M+) 85 (dec) (m, 5H), 4.48 — 4.29 (mm, 10), 3.45 (dd, J = 10.7, 6.4 He, 1H), 2.98 (dd, J = 10.7, 7.1
Hz, 1H), 1.26 (d, J = 6.3 Hz, 3H)
Two Isomers (CDCI3) & 8.56 (s, 21), 8.19 — 8.12 (m, 6H), 7.84 — 7.73 (m. LOH), 7.71 (d,
J=82Hz 2H), 7.47 (t, J = 8.0 Hz, 2H), . 626 n o 17.39(d, J=8.3 Hz, 41D), 4.76 ~ 4.64 (m, 160C J Mak) | PPO) IE 448 (dd, J = 14.6, 6.3 Hz, 1H), 3.43 (dd, J = 10.6, 6.2 Hz, 1H), 3.29 (dd, J = 10.5, 5.5 Hz, IID), 3.16 — 3.00 (m, 21D), 1.27 (d,J=6.4 He, 3H), 1.17 (d, J =6.4 Hz, 3H) (CDC13) 8 8.56 (s, LHD, 8.22 (s, 1H), 8.16 (d, J =8.4 Hz, 2H), 7.83 = 7.70 (m, 411), 566 105 7.39 (d, J =8.3 He, 2H), 6.94 (d, J =9.3 Hz, 161C J (M=+11) (dec) 2H), 4.43 - 4.22 (m, 111), 3.42 (dd, J = 10.8, 6.5 Hz, 1D), 3.00 (dd, J = 10).8, 8.5 Hz, 1H), 2.30 (s, 3HD, 2.25 (s, 3H), 2.21 (5, 3H), 1.20 (d, J = 6.3 Iz, 31) (CDCl) 8 8.56 (s, LH), 8.24 (s, 111), 8.17 (d, J =8.4 Hz, 2H), 7.83 = 7.73 (m, 4H), 568 (00 7.39 (d, J =8.3 Iz, 2IN), 7.13 = 7.09 (m, 162C J (MH) (dec) LID), 6.86 — 6.76 (m, 211), 4.33 - 4.19 (mm, 1H), 3.82 (s, 3H), 3.47 - 3.38 (im, 1H), 3.00 —2.99 (m, II), 2.29 -2.27 (m, 3ID), 1.33 — 1.15 (im, 3th)
Synthesis . orm 1 i (CDCly) 8 8.56 (s. 2H), 8.18 (dd, J = 10.7, 5.3 Hz, 6H), 7.84 — 7.74 (m, 8H), 7.42 — 7.30 (m, 811), 7.23 = 7.10 (m, 21), 4.37 (dd, 530 J=19.5, 13.6 Hz, 1H), 4.16 (dd, J = 13.1, 163C J stn | 92102 | 6.6 Hz, 111), 3.56 3.42 (m, 111), 3.34 (dd, J = 10.8, 6.0 tz, 11), 3.08 — 2.87 (im, 311), 2.70 (dd, J = 16.0, 7.0 Hz, 1H), 1.71 - 1.56 (m, 410), 1.34 = 1.25 (m, 611), 1.24 - 1.14 (m, 611), 0.93 = 0.73 (mn, 61D) (CDC) 8 8.56 (s, TH), 8.22 = 8.14 (m, 3H), 7.84 = 7.76 (m, 4H), 7.42 = 7.27 (m, 6H), 589 | 6.51 (t Jur =74.3 Hz, 1H), 4.52 = 4.31 (m, 164C ] viet) | 89) | 34d (ad, T= 10.8, 6.5 Hy, TH), 2.99 (dd, J = 10.8, 7.6 Hz, LH), 1.25 (d, J=6.3 . Hz, 3H)
Two Isomers (CDC13) 8 8.56 (s, 2H), 8.22 (s, 1H), 8.20 (s, 111), 8.16 (d, J = 8.3 Hz, 411), 7.84 — 7.74 (m, 8H), 7.58 (ddd, J =9.7, 8.0, 1.7 Hz, 2H), 7.39 (d, J = 8.4 Hz, 4H),
L65C | 530 [43 | 7.36-7.27 (m, 41D), 7.15 (dd, J =7.7, 1.6 o~ (M+H) (dec) | Hz, 1H), 7.09 (dd, J = 7.6, 1.7 Hz, 1H), 4.38 -4.22 (m, 2H), 3.61 (dd, J = 10.8, 7.0 Hz,
LI), 3.24 (dd, J = 10.7, 5.6 Hz, 1H), 3.07 — 2.94 (m, 1H), 2.91 (dd, J = 10.8, 1.5 Hz, 1H), 1.47 — 1.38 (m, 24H) (CDCl3) 3 8.56 (s, LL), 8.21 (s, LIT), 8.16 (d, J = 8.4 Hz, 2H), 7.84 —= 7.73 (1m, 4H), 552 7.39 (d, J = 8.3 Hz, 211), 7.32 = 7.28 (m, 166C J Malny | 93 (deo) | 311), 7.20 Gs, 1H), 4.20 — 4.06 (m, 1H), 3.41 (s, 1H), 3.05 (dd, J = 10.8, 8.2 Hz, 1H), 2.31 —32.30 (m, 3H), 1.66 (s, 2H), 0.90 — 0.88 (m1, 3H) ‘Two Isomers (CDCI3) 8 8.56 (5, 2H), 8.20 (s, 201), 8.16 (d, J = 8.3 Hz, 41), 7.83 = 7.74 (m, 8H), 7.43 — 7.28 (m, 611), 7.21 (dd, J = 586 105 | 5% 3.3 Hz, 4), 4.49 4.36 (m, 1H), 4.17 — 167C J Path (dey | +05 (m. 11D), 3.49 (dd, / = 10.7, 6.6 117, :
LH), 3.40 (dd, J = 10.7, 6.3 Hz, LED, 3.10 (dd, J=10.7,9.4 Hz, 1H), 3.04 (dd, J = : 10.8, 8.2 [1z, 1H), 2.34 (s, 3H), 2.30 (s, 3H), : 1.73 = 1.48 (m, 4H), 0.91 (im, 6H)
Synthesis op I I
ID Method MS mp (°C) LI NMR (8) (CDCIL3) 6 8.56 (s, 1H), 8.18 (m., 2H), 7.79
S60 (m, 411), 7.47 (dd, J = 7.8, 2.3 Hz, 1H), 7.42 168C J etsy | 199-200 | 7.32 (m, SID), 4.48 -4.29 (m, L11), 3.45 (dd, J = 10.7, 6.4 Hz, 1H), 2.98 (dd, J = 10.7, 7.1 lz, 1H), 1.26 (d, J = 6.3 Hz, 311) (CDC) 8 10.45 (s, LH), 8.59 (s, 11), 8.25 (d, J =8.3 Hz, 2H), 7.88 (d, J = 8.3 Hz. 2H), 7.81(d, J=8.9Ilz, 2), 7.61 (1. J = 7.5 Ha, i. 63 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.11 (t, J = 169C G (M+H) Oil | 8.0 Hz, 1H), 5.71 (d, J = 1.1 Hz, 1H), 2.35 (s, 310)
PF NMR (376 Miz, CDCly) 8 -58.02, - 62.31 (CDCL3) 3 8.56 (s, LH), 8.19 — 8.14 (m, 311), . 606 7.79 (m, 411), 7.56 — 7.46 (m, 211), 7.46 — -15¢ : ’ 170C G Mat) | P7159 743 (ml 21). 7.39 (0. J = 8.3 Hz, 2H), 5.88 (d, J=1.3 Hz, {H), 1.86 (d, J = 1.2 Hz, 3H) (CDCl3) 3 8.56 (s, LH), 8.19 (d, J = 5.9 Hz, ss3 2H), 8.16 (s, 1H), 7.83 — 7.76 (m, 4H), 7.45 171C G Sol) 236-237 | (tt, J = 8.4, 6.1 Hz, 1H), 7.39 (d, J = 8.3 lz, 2H), 7.10 (dd, J = 8.5, 7.3 Hz, 2H), 5.90 (d,
J=13 Hz, 1H), 1.92 (5, 3H) (CDCl) 8 8.56 (d, J = 3.7 Hz, 1H), 8.21 (s, 580 1H), 8.16 (d, J = 8.4 Hz, 2H), 7.84 — 7.72 172C G Mein | 103-108 | (m, 4H), 7.39 (d, J = 8.3 Hy, 2H), 6.72 6s, 2H), 5.89 (d, J = 1.3 Hz, 1H), 3.82 (s, 311), 2.14 (s, 611), 1.75 (d, J = 1.2 Hz, 3H). (CDCl3) 3 8.56 (s, 1H), 8.19-8.15 (m, 3H), , 536 7.82 — 7.75 (m, 411), 7.43 — 7.30 (m, 511) 173C G : » i, OL,
Mtn | 870) | od d= 73 Hy, LD). 5.88 (s, LID), 2.21 (s, 3H), 1.80 (d, J = 1.2 Hz, 3H) (CDC3) 5 8.56 (s, LH), 8.20 — 8.12 (m, 311), 70 7.83 7.74 (m, 411), 7.43 — 7.36 (in, 3H). 174C G Met | 95 (ee) | 732(L T= 7.7 Hy, 1H), 729-727 (m, 1H), 5.92(d, J = 1.3 Hz, IIT), 2.26 (s, 311), 1.81 d, J =12 Hz 3H)
; 3 : (CDCl) 88.56 (d, J = 5.0 Hz, 1H), 8.21 — 550 8.13 (m, 3H), 7.83 - 7.74 (im, 4H), 7.39 (d, J 175C G etn | 132-136 | = 82112211, 7.29 7.23 (m, UD, 7.19 d,
J=77 Hz, 2H). 5.92 (d, J = 1.3 Hz, 1H), 2.18 (s, 611), 1.75 (d, J = 1.2 Hz, 31). (CDCl) 58.56 (5, 1H), 8.19 — 8.14 (1m, 311), 7.83 — 7.75 (m, 4H), 7.49 — 7.43 (m, 2H),
S64 7.39 (d, J = 8.3 Tiz, 2H), 7.33 (ddd, J = 7.8, 176C G ty | 123138 | 59.3.0 Ha, 111), 7.19 7.17 (m, iD), 5.88 (d, J = 1.3 Hz, TH), 2.96 — 2.76 (im, 1H), 1.81 (d, J = 1.2 Ti7, 3H), 1.24 (t, J = 6.4 Hy, 3H), 1.22 = 1.16 (m, 311). (CDCl) 6 8.55 (s, 1H), 8.14 (d, J = 8.4 Hy, 211), 8.05 (s, 111), 7.84 — 7.77 (m, 211), 7.74 (d, J =8.3 Hz. 2H), 7.42 — 7.35 (m. 3H), 566 7.32 (dd, J = 10.6. 4.3 Hz, 1H), 7.08 — 7.24 tend vn | BIT 1, 7.18 (dd, J = 7.8, 14 117, 11D), 3.80 ~3.60 (mm, LH), 3.59 = 3.48 (m, 111), 3.11 (dd, T= 13.2, 6.8 Hz, 3H), 2.41 = 2.27 (m, 2H), 1.22 (t, J = 5.6 117, 6H). (CDCl3) 8 8.55 (d, J = 3.6 Hz, 1H), 8.14 (d,
J=8.4 Hz, 2H), 8.06 (s, 1H), 7.84 ~ 7.77 (m, 210), 7.74 (d, J = 8.4 117, 211), 7.38 (d, J } 580 = 0.0 Hz, 3H), 7.32 (id, J = 7.5, 1.4 Hz, 1H),
L78C J on | BOO a TH), 7.07 (4 T= 7.1 Hz, 1H), 3.60 — 3.26 (m, 111), 3.55 — 3.37 (mn, 111), 3.18 - 2.98 (m, 2H), 2.93 2.80 (m, 1H), 2.47 (d, J =35.9 Haz, 11D), 1.31 — 1.12 (m, OLY). (CDCl) 8 8.64 (s, 111), 8.15 (d, J = 8.4 I1z, 2H), 8.06 (s, 1H), 7.91 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 8.6 Tz, 21), 7.75 (d, J = 8.4 17, 550 2H), 7.38 (dd, J = 7.8, 1.6 Hz, 1H), 7.33 (1d, 179C J tn | 212213 | /=7.5, 14 Ha 1H). 7.29 - 7.23 (mn, TH), 7.18 (dd, J =7.8, 1.4 [17, 111), 3.78 — 3.72 (m, LH), 3.59 — 3.48 (m. 1H), 3.18 — 3.04 (m, 3H), 2.40 — 2.30 (m, 2H), 1.26 - 1.20 (m, 611). i
Synthesis os 1 i
ID Mothod MS mp (°C) [I NMR (8) (300 MHz, CDCLy) 8 8.55 (s, 1H), 8.13 (d, J = 8.3 Hz, 2H), 8.05 (s, 1H), 7.76 (dd, J = sec 17.0, 8.7 Lz, 411), 7.37 (1, J = 8.4 Hz, 211), 180C J arn | 127133 | 718 (dd. S=127,9.6 Hy, 31D, 3.54 - 3.49 + (m, 2H), 3.12 — 3.08 (m, 211), 2.70 - 2.55 (m, 2H), 2.39 = 2.31 (m, 211), 2.28 (s, 311), 1.25 (1, J = 7.6 Hz, 3H). (CDCl) 8 8.55 (s, 11), 8.14 (d, J = 8.3 [17 201), 8.08 (s, 111), 7.84 — 7.76 (m, 211), 7.74 582 1d, J=83 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 181C ] +n | TOV 665 (5, 211, 3.79 (5, 311), 3.52 — 3.45 (m, 210), 3.10 — 3.07 (m, 210), 2.38 = 2.31 (4, J = 5.7 Hz, 2H), 2.25 (s, 6H). (300 Miz, CDCly) 6 8.55 (d, J = 1.0 Hz,
LH), 8.14 (d, J = 8.4 Hz, 2H), 8.05 (s, 1H), 120C | 552 148-155; | 7.83 = 7.76 (m, 2H), 7.74 (d, J = 8.4 Hz, ot (M11) | 166-168 | 211), 7.38 (d, J = 9.0 [iz, 211), 7.14 = 7.09 (m, 3H), 3.51 (dd, J = 9.1, 3.5 Hz, 2H), 3.15 —3.03 (m, 2H), 2.36 (s, 2H), 2.28 (s, 6H). (CDCLy) § 8.55 (d, J = 3.7 Hz, 111), 8.14 (d,
J=8.4 Hz, 2H), 8.03 (d, J = 19.3 Hz 1H), 7.84 7.77 (m, 2H), 7.74 (d, J = 8.4 Hz, 210), 7.38 (d, J = 8.3 Iz, 211), 7.32 (d, J = 530 3.8 Hz, 2H), 7.25 (d, J = 6.6 Hz, LH). 7.19 183C J Mr iy | 159-162 | (1, =8.0 Hz, 1H), 3.76 (ddd, J = 24.2, 12.0, 5.9 Hz, U1), 3.58 — 3.46 (m, 111), 3.11 (dd, J = 15.3. 6.1 Hz, 2H), 2.82 (dd, J = 14.6, 7.2
Hz, IH), 2.41 — 2.29 (m, 211), 1.71-1.55 (m, 2H), 1.20 (d, J = 6.8 Hz, 311), 0.87 = 0.76 (m, 3H). (CDCl3) 8 8.55 (s, 1H), 8.14 (d, J = 8.4 117, 211), 8.07 (s, 1H), 7.83 = 7.76 (m, 211), 7.74 566 (d, J = 8.4 Hz, 2H), 7.40 (t. J = 10.1 Hz. 184C J 94. ty | 08a 6.03 (s, 200), 3.53 — 3.47 (m, 210), 3.12 ~3.05 (m, 2H), 2.34 (dL. J = 11.7, 5.8 1iz, 2H), 2.30 (s, 3H), 2.23 (s, 6H).
: ip | Synthesis MS | mp (°C) 'H NMR (3)’
Method (CDCls) 3 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.06 (s, 1H), 7.83 — 7.77 (m, 2H), 7.74 550 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 185C I Nip | 157-160 [7.36 7.27 (m, 31D), 7.23 ~ 7.19 (m, LH), ( 3.74 (m, 1H), 3.50 (m, 1H), 3.10 (d, J=5.9 | .
Hz, 2H), 2.64 (q, J = 7.6 Hz, 2H), 2.40 — 2.29 (m, 2H), 1.28 — 1.21 (m, 3H). (CDCl3) 8 8.55 (s, LI), 8.14 (d, J = 8.4 Hz, 2H), 8.09 (s, 1H), 7.83 — 7.77 (m, 2H), 7.81 seu ~7.77 (m, 2H), 7.38 (d, J = 8.3 Hz, 2H), 186C I apn | 173-177 | 7.24 27.22 (m, 3H), 7.05 - 6.95 (m, 1H), 3.77 — 3.63 (m, 2H), 3.14 — 3.07 (m, 2H), 2.45 2.29 (m, 2H), 2.09 — 1.92 (m, LH), 0.97 —0.82 (m, 3H), 0.53 (bs. 1H). (300 MHz, CDCl) § 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 4.9 Hz, 1H), 7.77 593 | (dd, J =11.4,8.6 Hz, 4H), 7.39 (¢, J = 8.1 rc) J oar | 180182 gy, Tay 721 (dd, T= 13.2, 5.6 Ha, 1H), 3.65 — 3.58 (m, 2H), 3.09 (t, J = 5.5 Hz, 2H), 2.45 — 2.35 (m, 211). (CDCl) 3 8.56 (s, LH), 8.15 (d, J = 8.4 Hz, 2H), 8.07 (s, LH), 7.79 (ddd, J = 15.8, 7.8, 576 5.8 Hz, 4H), 7.38 (d, J = 8.3 Hz, 2H), 7.31 — 212 188C I oH) | 299212 1991 (m, 2H), 7.10 (ddd, 7 =9.7. 7.8, 2.0 Hz, 1H), 3.64 (1, J = 5.4 Hz, 2H), 3.11 (t, J = 6.0
Hz, 2H), 2.46 — 2.33 (m, 2H). (CDCl3) 3 8.56 (5, 1H), 8.15 (d, J = 8.4 Hz, 560 2H), 8.08 (s, 1H), 7.83 — 7.74 (m, 4H), 7.38 189C J any | 217-219 | [J =83 Hz, 210), 7.31 = 7.21 (m, 1D), 7.03 - 6.94 (m, 2H), 3.72 — 3.62 (m, 2H), 3.15 3.07 (m, 2H), 2.40 — 2.34 (m, 2H). (CDCl) 8 8.55 (s, 1H), 8.14 (d, J = 8.3 Hz, 2H), 8.00 (s, LH), 7.83 — 7.73 (m, 4H), 7.71 626 (d, J =8.1 Hz, 1H), 7.67 (d, J = 7.7 Hz, 1H), 190C J ! eH) | P0193 900 ad, = 15.8, 8.2 Ha, 3H), 3.79 - 3.69 (m, 1H), 3.55 — 3.49 (m, 1H), 3.16 — 3.04 (m, 2H), 2.47 — 2.31 (m, 2H).
Synthesis . ° 1 1 (CDCly) 6 8.54 (d, J = 4.3 Hz, LH), 8.13 (d,
J=8.3 Hz, 2H), 8.05 (d, J = 6.3 Hz, LH), ss 7.77 (dd, J = 15.4, 8.7 Lz, 411), 7.38 (d, J = 191C J arn | 150-155 | 8.3 He, 2H), 7.29 (dd, J = 8.0, 4.8 He, 20D), ) 7.04 — 6.93 (m, 211), 3.85 (s, 311), 3.65 — 3.61 (m, 2D, 3.10 - 3.06 (m, 2k), 2.36 — 2.28 (s, 2H). (CDCl) 3 8.55 (s, 111), 8.14 (d, J = 8.4 117, 211), 8.09 (s, LID), 7.82 — 7.77 (im, 211). 7.74 oo 1d, T= 6.7 Hy, 2H), 7.38 (d, J = 8.3 Hz, 2H), 192C J oro 7.13 (d, J = 8.3 Hz, 111), 6.79 (dd, J = 1 1.9, 13.3 He, 21D, 3.81 (s, 3H), 3.74 - 3.66 (m,
LH), 3.57 — 3.48 (m, 1H), 3.12 — 3.04 (m, 211), 2.36 — 2.30 (m, 2H), 2.25 (s, 3H). (CDCl) 8 8.55 (s, LH), 8.14 (d, J = 8.4 Hz, 2H). 8.04 (s, 1H), 7.83 = 7.77 (m. 2H), 7.74 (d, J = 8.4 Hz, 211), 7.38 (d, J = 8.3 Hz, 211), am 580) 7.31 ~7.24 (m, 3H), 7.23 — 7.20 (m, 11), -15 193€ ! ost) | P8380 371 (mn, 1H), 3.56 — 3.47 (mn, 1H), 317-302 (m, 21D, 2.46 (t, J =6.7 Hz, 2H), 2.39 — 2.27 (m, 2H), 1.99 (heptet, J = 6.8 Hz, 1H), 0.95 - 0.92 (m, 6H). (CDC13) 3 8.56 (s, 11), 8.17 (m 310), 7.80 600 oo | (m, 4H), 7.52 — 7.47 (m, 2H), 7.47 — 7.31 04 3 \ ’ 194C ! oan | 0108 om), 3.42 — 3.08 (m, 28D), 2.86 (bs, 2H), 2.04 = 1.71 (m, 211). (CDCl3) 6 8.55 (s, LH), 8.14 (dl, J = 8.3 Hz, 2H), 8.08 (s, 1H), 7.84 — 7.77 (m, 2H), 7.75 <n 538 (d, J = 8.4 Hz, 211), 7.38 (d, J = 8.5 Hz, 2H), ¢ 9.162 195C ! MH) | P2102 1731 27.19 (m, 4H), 3.81 - 3.47 (mn, 2H), 3.20 — 3.00 (m, 211), 2.35 (dt, J = 11.7,5.8
Iz, 211), 2.28 (s, 3H). (CDCly) § 8.55 (s, LH), 8.14 (d, J = 8.1 Hz, 21), 8.05 (s, 1H), 7.80 (d, J = 8.9 Hz, 2), 573 7.75 (d, J =8.2 Hz, 211), 7.38 (d, J = 8.8 Hz, 196C J (Mein | 140-143 | 2H), 7.33 (4d, J = 6.1, 3.4 Hy, 1H), 7.21 - 7.15 (m, 211), 3.72 — 3.66 (m, 111), 3.55 — 3.41 (im, 1H), 3.16 — 3.05 (mm, 21), 2.48 — : 2.34 (m. 2H), 2.32 (s, 3H).
Synthesis . 0p i I (CDCl) 8 8.55 (s, 1H), 8.14 (d, J = 8.2 Hz, 2H), 8.06 (s, 1H), 7.80 (d, J = 8.9 Hz, 21), 574 7.75 (d, J = 8.2 Hz, 211), 7.38 (d, J = 8.8 iz, ; 197C J Me) | 51155 | 2HD.7.29 (dd, 1 = 10.7, 4.6 fle, 4H), 6.20, 11), 3.50 — 3.48 (m, 211), 3.10 — 3.01 (m. 211), 2.34 — 2.20 (m, 2H), 1.90 (s, 311), 1.78 (s, 3H). (CDCL3) 8 8.56 (s, 111), 8.36 (dd, J=4.8, 1.3
Hz, LID), 8.15 (d, J = 8.3 11z, 211), 8.09 (s, $39 1H), 7.78 (im, 4H), 7.54 (dd, J = 7.5, 0.9 Hz, 198C J rt 186-189 | LID), 7.37 (d, J = 8.5 Hz, 211), 7.13 (dd, J = 7.4,4.8 He, 11), 3.87 (1, J = 5.7 Hz, 2H), 3.12 = 3.03 (m, 2H), 2.40 — 2.32 (m, 2H), 2.24 (s, 31D). (CDCl3) 8 8.55 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.05 (s, 1H), 7.83 — 7.78 (m, 2H), 7.76 , 608 (d, J =8.4 Hz, 21D), 7.43 — 7.36 (mm, 311), 9 27-208 199C ] oak) | 297208 | 93a 72 a7 He, 36D, 3.71 — 3.64 (um. 2H), 3.12 — 3.06 (m, 2H), 2.39 — 2.30 (im, 2H). (CDCl3) 8 8.56 (s, LH), 8.15 (d, J = 8.4 Hz, 590 2H), 8.03 (s, 1H), 7.83 = 7.77 (m, 2H), 7.76 200C J Malp | 170-172 | (d, J =83 Tz, 21D), 7.42 - 7.27 (um, 61), 6.74 — 6.29 (mm, 1H), 3.70 — 3.64 (m, 2H), 3.13 3.06 (m, 21), 2.40 - 2.31 (m, 2H). (CDCl) 8 8.55 (s, 1H), 8.14 (d, J = 8.3 Hz, 2H). 8.00 (s, 1H), 7.83 = 7.73 (m, 4H), 7.71 ; 626 . 1d, 7=8.117 1H), 7.67 (d, J =7.7 Hz, 1H), 2 _ My ; 201€ I etn | 0193540 (dd, J = 15.8, 8.2 Lz, 311), 3.79 — 3.60 ; (m, 1H), 3.55 — 3.49 (m, 1H), 3.16 — 3.04 (m, 211), 2.47 — 2.31 (m, 2H). (CDCI3) § 8.56 (5, 111), 8.19 — 8.08 (m, 310), ssa 7.84 7.72 (m, 4H), 7.39 (d, J = 8.4 Hz, 202C (Marry | 231-234 | 2H). 7.25 7.20 (m, 2H), 6.96 - 6.88 (m, 211), 3.83 (s, 311), 3.76 = 3.68 (m. 211), 3.13 = 3.03 (im, 2H), 2.39 — 2.27 (in, 2H).
:
Synthesis . 0 0
ID Method MS mp (°C) [I NMR (&) (CDCL) 8 8.56 (s., LH), 8.15 (d, J = 8.2 Haz, 2H). 8.06 (s, LID), 7.83 — 7.77 (m, 2H), 7.75 631 | | (d J =821z 2H), 7.39 d, J = 8.5 Hz, 211), 203¢ J +t | 299200 598 795 (mL 26D. 3.51 - 3.42 (m. 20D), 3.14 - 3.05 (m, 211), 2.35 (s, 21D), 2.25 (s, 61D). (CDC) 68.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 201), 8.00 (s, 111), 7.84 — 7.77 (m. 211), 7.75 563 ds =8411z, 211), 7.38 (d, J = 8.3 11, 21D), 314 GRC 204C J ov) | 390 1308 (1 T= 4.0 Hz, 2H), 6.88 (d. J = 8.6 Hy,
LID). 3.82 (s, 311), 3.66 — 3.58 (m, 211), 3.11 —~3.03 (m, 2H), 2.36 — 2.27 (m, 5H). (CDC) 58.55 (s, 1H), 8.45 (dd. J =4.8, 1.6
Hz, 11D), 8.18 — 8.12 (m, 211), 8.06 (s, 111),
S10 7.82 7.72 (m, 4H), 7.53 (dd, J = 7.9. 1.6 2050 J Ah Oil | Hz, ET), 7.40 — 7.33 (m. 2H), 7.24 7.18 (m, L110), 3.63 (brs, 2H), 3.18 — 3.03 (m, 2H), 2.51 (s 3H. 2.35 (dL. J = 11.7. 5.7 Hz, oH) (CDCly) 38.56 (s, 1H), 8.16 (d, J = 8.9 117, 3H), 7.84 — 7.73 (im, 4H), 7.39 (d, J = 8.3 554 Tz, 2H), 7.30 (t. J = 8.1 Hz, 1H), 6.95 — 7 _ g \ ? g 2060 I ovetty | 78 6s tm, 211), 6.78 (dt J= 11.1, 5.5 Ha,
LH), 3.81 (s, 3H), 3.79 = 3.73 (mn, 2H), 3.12 ~3.04 (m, 2H), 2.38 — 2.28 (m, 2H). (CDCl) § 8.57 (s, 1H), 8.23 — $.13 (m, 31), 8.06 (d, J = 8.5 Hz, 211), 7.80 (dd. J = 8.5, 506 | 4.5 THz, 411), 7.39 (d, J = 8.5 Hz, 41), 4.38 7 _ 207C I ast) | V3 S720, 21, 3.82 (1 J = 6.0 Liz, 210), 3.14 — 3.03 (m, 2H). 2.37 (s, 2H), 1.40 (t. J =7.1 Hz, 3H). (CDCly) 58.55 5. 111). 8.14 (d. J = 8.3 112, 2H), 8.07 (s, LH), 7.84 — 7.77 (m, 2H). 7.75 (d, J =8.3 Hz, 211), 7.38 (d, J = 8.3 Hz, 2H), . 563 7.32 -7.23 (m, 2H). 6.99 (ddd, J = 8.3. 5.5 208C } 8 J ory | EY hy, 91), 4.08 (g, J = 7.0 Hy, 2H). 3.69 - 3.57 (m, 201), 3.16 — 3.02 (m, 211), 2.32 (dk,
J=117.5.9 Hz, 28D). 1.39 (1. J = 7.0 He, 3H). :
..
Method (CDCy) 8 8.64 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.06 (s, 11D), 7.91 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.4 11z, 550 2H). 7.38 (dd, J = 7.8, 1.6 Hz, 111), 7.33 (1d, 209C J (MH) 212-213 | J=17.5, 1.4 Hz, 1D), 7.29 ~ 7.23 (m, LID), 7.18 (dd, J =7.8, 1.4 Hz, LH), 3.78 - 3.72 (m, 1H), 3.59 - 3.48 (im, 1H), 3.18 = 3.04 (m, 3M), 2.40 - 2.30 (m, 21D), 1.26 — 1.20 (m, 611). (CDC) 3 8.55 (s, 1H), 8.14 (d, J = 8.4 Hy, 211), 8.07 (s, LID), 7.83 — 7.77 (m, 2H), 7.75 (d, J = 8.4 Hz, 281), 7.55 — 7.49 (m, 1H), 530) 7.38(d,/J=83 Hz, 2H), 7.32 - 7.26 (m, 210C J M11) 136-139 | 2H), 7.19 = 7.13 (m, LH), 3.72 (ddd, J = 12.9, 9.3, 3.8 Lz, 111), 3.60 - 3.51 (m, LI), 3.15 (ddd, J=13.3,9.4, 4.0 Hz, 1H), 3.10 - 3.00 (my 1H), 2.51 =2.36 (m, 111), 2.36 — : 2.22 (m. 1H). 1.43 (s, 9H). (CDCI3) 8 8.55 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.10 (s. IHD), 7.79 (dt, J = 10.4, 5.8 Hz, 566 4H), 7.38 (d, J = 8.3 Hz, 2H), 7.11 (s, 3H), 2c I over | 00106 39s 3 98 (my 2H), 3.20 — 3.12 (m, 2H), 2.30 (s, 611), 2.13 = 2.07 (m, 21D), 1.87 — 1.82 (m, 2H). (CDC13) 8 8.55 (s, 1H), 8.19 — 8.10 (m, 3H), 7.79 (dt, J = 10.7, 5.9 Hz, 411), 7.38 (dd, J = 530 8.5,2.6 Hz, 3H), 7.30 (ud, J= 7.5, 1.4 Hz, 212C I (MD) 186-188 | 1H), 7.23 (td, J =7.5, 1.7 [1z, LI), 7.13 (dd,
J=17.8, 1.4 Hz, 1H), 3.94 (bs, 211), 3.24 — 3.02 (m, 3H), 2.13 = 2.05 (m, 2H), 1.84 — 1.73 (m, 2H), 1.24 (t, J = 10.5 Hz, 611). ; (CDCl) 8 8.55 (s, LID), 8.13 (d, J = 8.4 11z, : 2H), 8.03 (d, J =4.4 Hz, 1H), 7.83 - 7.76 : (m, 210), 7.74 (d, J = 8.0 Iz, 2H), 7.38 (d, J : 213¢ ] 580 173.127 | = 8:4 Hz, 21D), 7.24 ~ 7.15 (m, 211), 7.12 (M+H) TT (dd, J =11.9,4.6 Hz, TH), 3.82 = 3.71 (in,
HD, 3.30 - 3.18 (im, 11), 3.07 - 2.94 (m, 1H), 2.72 = 2.40 (m, 3H), 2.30 — 2.16 (m, 4H), 1.30 = 1.12 (m, 6H).
; . (CDC13) 8 8.55 (s, LH), 8.15 (d, J = 8.4 Hz, 2H), 8.06 (s, 1HD, 7.83 ~ 7.72 (m, 4H), 7.38 (m, 311), 7.34 (dd, J = 2.9, 1.5 Lz, 311), 3.58 622 (ddd, J =12.3, 3.9, 1.4 Hz, 110), 3.39 (dd, J 214C J Merny | 1001620 0 9011 1H, 3.04 (ddd, J = 12.2, 3.9.
L.4 Hz, tH), 2.84 (dd, J = 12.2, 9.5 Hz, 111), 2.61 2.42 (m, 1H), 1.18 (d, J = 6.7 Hz, 31D (CDCl) 38.55, LH), 8.14 (dd, J=8.3, L.5
Hz, 2H), 8.00 (d, J = 4.0 Hz, 1H), 7.84 — 640 He | 772 (m, 41D), 7.72 7.63 (m, 2H), 7.45 ~ 215C J (MH) (deo) 7.32 (my, 3H), 3.60 — 3.44 (im, 111), 3.37 — 3.27 (m, 1H), 3.03 = 2.92 (m, 1H), 2.92 — 2.82 (m, 1H), 2.69 — 2.54 (m, IF), 1.19 —
L112 (m, 31) (CDCI) 8 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H). 8.02 (s, LIT), 7.82 — 7.71 (m, 411), 7.44 622 ~7.30 (nm. 6H), 3.87 (d, J = 6.3 Hz, 1H), 216C J (MIT) 132-135 | 3.23 (td, J= 11.9, 3.8 Hz, 1H), 3.07 - 2.94 (m, 110), 2.54 — 2.43 (m, LH), 2.19 (ddd, J = 13.9, 9.0, 5.0 Hz, LH), 1.31 (d, J = 6.6 Hz, 3H)
Two isomers (CDCls) 8 8.55 (s, 210), 8.14 : (dd, J =8.4,2.7 Hz, 4H), 7.98 (d, J =4.2 :
Hz, 2H), 7.83 = 7.72 (m, 8H), 7.67 (dt, J = 640 12.9, 7.4 Hz, 4H), 7.40 (dd, J = 15.3, 8.1 : 217C J (MH) 93 (dec) | Hz, 6H), 4.17 (s, 1H), 3.96 (td, J = 6.6, 3.1
Hz, LF), 3.24 = 3.12 (m, 2H), 3.12 = 3.01 (m, 21), 2.41 (dddd, J = 10.8, 10.0, 8.9, 4.2
Hz, 2H), 2.30 = 2.15 (m, 2H), 1.24 (d. J = 6.7 Hz, 310), 1.04 (d, J = 6.7 Hz, 311) (CDCl5) 8 8.55 (s, 111), 8.18 — 8.10 (m, 211), 8.05 (s, LH), 7.83 — 7.76 (m, 2H), 7.73 (d. J = 8.4 Hz, 211), 7.41 7.37 (m, 211), 6.93 (d, . 580) Co | J=9.4 Hz 2H), 3.76 (dd, J = 10.8, 4.6 Hz, 218C ! MH) | 22 1329 13.16 (m, 1H), 2.99 (ddd, J = 12.2,5.9,3.91Tz, 1H), 2.54 - 2.37 (m, IID), 2.31 (s, 311, 2.22 (d, J = 6.4 Hz, 7H), 1.19 : (d, J =6.7 Hz, 3H) 153 E j (CDCI3) 8 8.55 (s, LH), 8.14 — 8.06 (m1, 3H), 7.91 - 7.65 (m, 4H), 7.44 — 7.37 (m, 2H), 2190 ; 592 100 | 7.16 = 7.09 (m, 111), 6.93 - 6.77 (m, 211), = (M+H) (dec) | 4.06 -3.64 (m, 4H), 3.31 — 3.16 (m, 1H), 3.02 -2.92 (m, 1H), 2.51 — 2.40 (m, 111), 225-217 (m, 41D), 1.41 - 1.14 (m, 31D
Two isomers: (CDCly) 8 8.55 (s, 1H), 8.16 — 8.00 (m, 21), 8.01 (m, 11), 7.86 — 7.76 (m, 211). 7.76 = 7.70 (1n, 211), 7.64 — 7.28 (m, 4H), 7.24 = 7.14 (in, 2H), 4.08 — 3.65 (m. 593 LHD, 3.37 = 3.15 (m, 11D), 3.09 = 2.92 (m, 220C ! Mh | 239 280 (LJ = 14.2, 6.8 Hz, 1H), 2.45 m, 1H), 2.35 = 2.09 (m. 1H), 1.76 — 1.58 (m,
LH), 1.48 = 1.35 (m, 210), 1.27 = 1.19 (m, 2H), 119 — 1.13 (m, 2H), 1.06 — 0.92 (m,
PHD. 0.92 = 0.72 (m, 3H) : (400 Mllz, CDC15) 8 8.56 (s, 111), 8.20 — 8.10 (m, 2H), 8.00 (s, 1H), 7.83 = 7.77 (im, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.42 - 7.28 2c J 603 113 (m, 611), 6.72 ~ 6.25 (m, LH), 3.90 (d, J = : “= (M+H) (dec) | 6.4 Hz, 1H), 3.24 (ud, J = 12.0, 3.6 Hz, 1H), 3.05-2.93 (m, 1H), 2.49 (it, J= 11.7, 4.0
Hz, 1H), 2.21 (td, J = 8.7, 4.4 Hz, LH), 1.29 : (d, J = 6.6 Hz, 3H) (CDC) § 8.55 (5, 1H), 8.14 (dd, J =8.4, 2.1 lz, 210), 8.05 (d, J = 2.8 l1z, 111), 7.87 ~ : 7.72 (m, 4H), 7.61 — 7.49 (m, 1H), 7.38 (d, J 0 ] 594 124 | =8.3 Hz, 2H), 7.33 — 7.21 (m, 21), 7.15 — rr (M+) (dec) 7.05 (m, 1H), 3.79 - 3.68 (m, 1H), 3.51 — : 3.29 (in, 1H), 3.12 —2.93 (m, 1H), 2.66 — 2.52 (m, TH), 2.18 = 2.12 (m, 11), 1.43 (m, : 1211) (CDCl5) 8 8.58 (s, 1H), 8.21 (d, J = 8.4 Hz. 566 2H), 8.16 (s, 111), 7.85 — 7.77 (m, 411), 7.40 { 223( L (MHD) 75-87 | (d, J =8.3 Hz, 211), 7.23 (dd, J = 8.4, 6.6
Hz, 1H), 7.15 (d, J = 7.5 Hz, 2H), 3.24 — f 3.14 (m, 411), 2.18 (s, 6H).
Synthesis . of | !
P| Yiethod MS mp (°C) 11 NMR (8) (CDCLy) 8 8.57 (s. LH), 8.21 (d, J = 8.4 Hz, 2H), 8.16 (s, 1H), 7.85 — 7.75 (m, 41), 7.46 204c 530) 118 | =7.36 (im, 411), 7.33 = 7.26 (m, 111), 7.10 (d, “= - (M+11) (dec) | J=7.6 Hz, 1H). 3.26 — 3.14 (m, 411), 2.81 (sept, J = 6.9 Hz, LID), 1.21 (t, J=7.2 Hz, 611). (CDCl) 5 8.57 (s, LH), 8.21 (d, J = 8.4 Hz, 2H), 8.15 (s, 111), 7.86 — 7.76 (m, 411), 7.39 ye L 530 LIT | (d, J=8.3 lz 211), 7.29 (t, J = 7.6 11z, 11), (M+H) (dec) 721 7.15 (m, 2H), 3.27 = 3.10 (m, 4H), 2.50 (q, J = 7.5 fz, 21), 2.18 (s, 311), 1.20 (t, J =7.6 Hz, 3H). 573 (CDCL3) 8 8.57 (s, TH), 8.24 - 8.16 (m, 3H), 226C I (Vel) | 196-200 | 7.85 7.76 (m, 411), 7.43 ~ 7.34 (m, 311), 7.03 (dd, J = 8.5, 7.4 Hz, 2H), 3.21 (s, 411) (CDC3) 8 8.57 (s, 1H), 8.21 (d, J = 8.3 Ho, 2M), 8.15 (s, 111), 7.81 (t, J = 9.1 Tz, 411), 217¢ L 386 Oil | 743-731 (m, 310), 7.28 = 7.21 (m, 21), (M+H) 3.36 = 3.07 (m, 4H), 2.24 (s, 3H): "”F NMR (376 M117, CDCly) 8-58.02 (CDCl3) 8 8.57 (s, LH), 8.21 (d, J = 8.3 Hz, 640 2H), 8.11 (s, 1H), 7.81 (dd, J = 11.5, 4.7 Hz, 228C L MD) 99 (dec) | 4H), 7.72 (dd, J = 17.3, 8.0 Hz, 2H), 7.51 (dd, J = 10.0, 5.4 Hz, 11), 7.39 (d, J = 8.3
Hz, 2H), 3.36 — 3.03 (m, 4H) (CDCl3) 8 8.57 (s, LTD), 8.21 (d, J = 8.4 Hz, . 622 | 21D, 8.13 (s, LH), 7.80 (dt, J = 5.5, 4.9 Hz, ole] . . s er Lb M+) | 2219) 41 7.44 27.34 (m, 6H), 3.29 — 3.10 (m, 417) (CDCl3) 8 8.57 (s, 1H), 8.21 (d, J = 8.3 Iz, 2H), 8.14 (d, J = 15.4 Hz, 1H), 7.83 — 7.76 504 (m, 411), 7.43 — 7.37 (m, 410), 7.32 = 7.26 230C L (Mab | 94 (ee) | (m, 1D, 7.16 7.09 (m, 111), 3.24 - 3.12 (m, 4H), 2.61 — 2.44 (m, 1H), 1.75 = 1.50 (m, 211), 1.17 (dd, J = 6.9, 3.3 117, 311), 0.87 0.73 (m, 3H)
Synthesis . o | onl
ID Method MS mp (°C) EH NMR (3) (CDCI) 8 8.58 (s, LH), 8.22 (s, 1H), 8.19 <r 0s | 7=50H,2H),781 (dd, J=87,55 23I1C L SLD | dee | 4D. 740 (dS =8.3 112,210, 7.05 @, J : =8.3 Hz. 1H), 6.90 — 6.76 (im, 2H), 3.83 (s, 3H), 3.22 — 3.11 (m, 411), 2.16 (s, 311) (CDCl) 88.57 (5, 111), 8.21 (d, J = 8.4 117, 2H), 8.16 (s, LH), 7.81 (dd, J = 8.7, 5.3 Hz, ric 593 120 | 411),7.58 (dd, J = 8.1, 1.5 Hz, 11), 7.38 3c (M+) | (dec) | (dd, J = 13.2, 5.1 Hz, 3H), 7.33 — 7.27 (m.
LH), 7.02 — 6.96 (m, 1H), 3.37 =3.01 (m, 410), 1.36 (s, 91D) (CDC) 8 8.58 (s, LH), 8.21 (d, J = 8.4 Lz, 604 2H), 8.14 (5, 1H). 7.86 — 7.72 (m, 4H), 7.48 9 7} PN 233€C I Man | 22 08 im, 611), 6.40 (t, Je = 743 Ha, 111), 325-311 (m, 4) (300 MHz, CDCl) § 8.57 (s, 1H), 8.31 (5, sis | 113.116 | 1TD-821 (5, IHD), 8.18 (5, 111), 786 7.76 240C J MED (m, 411), 7.48 — 7.31 (m, 4H), 7.31 = 7.20 (m, 2H), 4.92 (s, 2H), 3.42 - 3.27 (m, 1H), 1.31 (s, 311), 1.28 (s, 3H) (CDCl) 5 8.56 (5, 1H), 8.20 (s, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.83 — 7.76 (m, 4H), ou 7.39 (d, J = 8.3 Hz, 21D), 7.18 (dd, J = 8.4, 241C J (VAD Oil | 6.6 Hz 1H), 7.09 (d. J = 7.7 Hz, 2H), 4.87 (s, 2FD), 2.40 (s, 61D);
YI NMR (376 MHz, CDCl) § -38.04 (CDCl) 6 8.57 (s, LH), 8.30 (s, 111), 8.19 554 co | (d,7= 8.3 Hz. 2H), 7.84 = 7.76 (m, 4), 240 _ - :
HA vein | 91930 4,783 11, 210), 6.62 5,211), 4.34 (s. 2H), 3.78 (s, 3H), 2.37 (s. 6H) (CDCl) 58.57 (s, 1H), 8.29 (s, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.85 — 7.76 (m, 411), : 538 7.39 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 7.6 Hz, 243C ] iC ! +H) | PUI, 7.17 27.08 (m, 2H), 4.88 (q, 7 = 4.1
Hz, 2H), 2.87 = 2.65 (m, 211), 2.40 (s, 31D), 1.28 (t, J = 7.5 Hz, 3H) (CDCl) 58.57 Cs, 1H), 8.31 (5, 1H), 8.19
J 564 (d, J =8.31lz, 2D), 7.83 — 7.79 (mm, 411), : 244C i ! +n | 4188 740 738 (ak, 731 - 7.27 (m, LH), 5.02 (s, 2H) ;
Synthesis or I onl (CDCI) § 8.58 (s. LH), 8.34 (s. LH), 8.20 532 Co 1, J=8.3 Hz, 2H), 7.81 (d, J = 8.8 Hz, 4H), 245C ! Meth | 040 (T= 83 Tz, 211), 7.31 = 7.23 (m,
LH), 7.03 — 6.97 (m, 2H), 5.05 (s, 2H) (CDCl) 8 8.57 (s, 111), 8.30 (s, 111), 8.19 sad (d, J =8.3 Hz, 21), 7.84 — 7.77 (m, 411), 2460 J vy | 157-1601 7.39(d, J = 8.2 Hy, 2H), 7.34 - 7.28 (m, (M-+H) 111), 7.25 = 7.15 (m, 211), 5.19 (s, 111), 4.81 (s, LED), 2.46 (s, 311) (CDC5) 8 8.58 (s, 1H), 8.31 (s, 1H), 8.20 (d, J =8.4 117,211), 7.86 — 7.78 (im, 411), 7.49 — 7.28 (m, 5H), 7.26 - 7.21 (m, 1H), 587 4.93 (s, 2H), 3.35 (dt, J = 13.7, 6.9 Hz. 110),
MIC I M+ | 728 11 30(d T= 69 112. 61D):
F NMR (376 MHz. CDC13) § -85.90, -87.84 (CDCl3) 3 8.60 — 8.58 (m, 1H), 8.28 — 8.14 (m, 2I), 8.00 — 7.91 (m, 211), 7.82 (tdd, J = 5.5,3.5, 1.7 Hz, 2H), 7.53 = 7.25 (m, 4H), ss 7.11 = 6.91 (m, 2H), 4.94 (s, 2H), 3.26 (dt, J 248C J PR = 13.8, 6.9 Hz, 1H), 2.60 — 2.37 (m, 31), (IM+1L]Y 1.31 - 1.17 (m, 6H);
YE NMR (376 MHz, CDCl) & 58.02 (CDCl) 8 8.53 (s, 11), 8.31 (s, 11), 8.18 (d, J = 8.3 Hz, 211), 7.80 (d, J = 8.3 Hz, 2H). 7.57 (A. J=2.1 Hz, 1H), 7.50 — 7.43 (m, 310), 7.33 (dtd, J =9.1,7.8, 1.5 Hz, 21D), . 533 7.21 (ddd, J = 13.8, 7.9, 3.5 Hz, 2H), 4.93 24¢ 3. 249C ! aH | 7370 | (6 2), 341-327 (m, TH), 1.30 (d. J = 6.9
Hz, 611); I
F NMR (376 MHz, CDCI) 8 -49.65 (DMSO-ds) 59.44 (s, 1H), 8.27 (s, 1H), 8.21 — 8.12 (m, 2H), 8.13 — 8.06 (m, 211), 7.85 =7.75 (m, 2H), 7.67 — 7.60 (m, 211), ] sss 7.46 (td, J=8.1,5.8 Hz, 1H), 7.18 — 7.31 250C J (MAH) (m, 211), 5.05 (s, 211), 3.22 ~ 3.32 (m, 111), 1.25 (d, J = 6.8 Hz, 6H): 91 NMR (376 MIlz, DMSO-dq) & -56.95, -120.51 :
: (DMSO-d) 4 9.44 (s, 1H), 8.32 (s. 1H), 821 -8.13 (m, 21), 8.13 — 8.05 (m, 2H), 7.89 = 7.79 (m, 210), 7.70 — 7.59 (im, 211), 555 7.54 — 7.40 (m, 2H), 7.19 (ld, J = 8.5, 2.8 251C J AMAL) Hz, 11D), 5.16 (s, 210), 3.29 (hept, J =6.9
Hz, 1H), 1.23 (d, J = 6.8 Hz, 6H); 1 NMR (376 Milz, DMSO-d) 8 56.97, -115.87 (DMSO-de) 9.44 (s, 111), 8.28 (s, | F1), 8.21 —8.13 (m, 2H), 8.13 — 8.05 (m, 211), 7.85 - 7.78 (m, 2H), 7.67 — 7.61 (m, 2H), 7.58 (dd, J =8.8, 5.6 Hz, 111), 7.26 (dd, J = 350 | 555 10.4, 3.0 He, 1H), 7.12 (ddd. J = 8.8, 8.0,
BE (IM+HTH 3.0 Hz, 1H). 5.10 (s, 2H), 3.32 = 3.21 (m,
Lin, 1.24 (d, J = 6.8 Iz, 6113;
YF NMR (376 MHz, DMSO-ds) & 56.96, -112.55 (DMSO-d) $9.43 (s, 1H). 8.30 (s, 1H), 8.18 = 8.12 (m, 2H), 8.12 — 8.05 (m, 2H). 7.85 7.77 (m, 2H), 7.68 — 7.58 (im, 2H), 7.40 (dd, J =8.0, 1.3 Hz, 1H), 7.32 (td, J = "530 ; 555 8.1,5.9 Hz, 111), 7.17 (ddd, F= 11.7, 8.2, =o (M+H[" 1.3 Hz, LH), 5.13 (s, 2H), 3.32 — 3.23 (m, 1H), 1.35 (dd, J = 7.0, 1.3 Hz, 6H):
EF NMR (376 MHz, DMSO-d) & -56.96, -112.92 : (DMSO-d) 3 9.46 (s, 111), 8.34 (s, LI), 8.22 - 8.15 (m, 2H), 8.15 = 8.06 (m, 2H), 7.90 — 7.80 (m, 2110), 7.70 — 7.62 (m, 2H), 573 7.63 — 7.55 (mn, 1H), 7.42 — 7.24 (m, 3H). 254C J (MAH) 5.16 (s, 2H), 2.79 (4, J = 7.5 Hz, 2H), 1.24 (t, J =17.51lz 31); "°F NMR (376 MHz, DMSO-d) 3 : -56.95 (DMSO-ds) $9.57 (s. 1H). 8.33 (s, 1H), 8.26 — 8.12 (m, 41D), 8.05 — 7.95 (m, 211), 7.89 7.79 (m, 2H), 7.55 — 7.39 (m, 2H), 530 7.19 (td, J = 8.5, 2.8 Hz, 1H), 5.16 (s, 2H), 255C J Re 3.23-3.32 (m, LID), 1.23(d, J = 6.8 117, (IM+H]%) : 6H);
YE NMR (376 MIlz, DMSO-d) & : -60.81, -115.86
Synthesis , om 1 !
ID Method MS mp (°C) II NMR (§) (DMSO-d) 69.45 (s, 1H), 8.32 (s, 1H), 8.20) - 8.14 (m, 2H), 8.14 — 8.07 (m, 2), 7.91 =7.78 (m, 2H), 7.68 — 7.59 (m, 211), (05 7.47 (ddd, J = 15.2, 9.4, 4.6 Hz, 2H), 7.19 256C J AML) (td, J =8.5,2.8 Hz, IIT), 5.16 (s, 211), 3.32 — 3.24 (m, 1H), 1.23 (d, J = 6.8 Hz, 6H); 1 NMR (376 MIlz, DMSO-dg) & -85.18, -86.91, -115.87 (DMSO-d) 59.54 (s, 111), 8.33 (s, 11D), 8.29 - 8.21 (m, 21D), 8.21 — 8.15 (m, 21D), 7.93 (d, J = 8.5 Hz, 2H), 7-89 -7.79 (m, 2H), 7.47 (ddd, J = 15.1, 9.4, 4.6 I17, 21), 7.19 639 (td, J =8.5,2.8 Hz, 111), 5.16 (s, 2H), 3.32 — 257C J 13 2 CTRL = AM+H]H 3.23 (m. 1H), 1.23 (d, J = 6.8 Hz, 6H;
PI NMR (376 MIlz, DMSO-d) 5 275.06 (d, J = 7.5 Hz), -115.87, -181.30 (p. J =7.8 Hz) (DMSO-d) 89.55 (s, 111), 8.33 (s, 11D), 8.28 — 8.20 (my, 2H), 8.21 —- 8.15 (im, 2H). 7.98 — 7.89 (m, 211), 7.88 — 7.80 (m, 2H), 7.47 (ddd, J = 15.2, 9.4, 4.6 Hz, 211), 7.19 50 (td, J = 8.5,2.8 Hz, 1H), 5.16 (s, 2H), 3.31 - 3.25 (m, 1H), 1.23 (d, J = 6.8 Hz, 61); 258C I (IM+11]%)
FE NMR (376 MHz, DMSO-d) 8 72.98 —-73.71 (m), -78.73 (d, J = 12.8 Hz), -115.87,-120.53 — -121.42 (m), -182.23 (dt, :
J =257.15.5 Hz) (DMSO-ds) 59.49 (s, 111), 8.32 (s, 111), : 8.24 — 8.13 (m, 2H), 8.12 -8.03 (m, 211), 7.91-7.75 (m, 4H), 7.47 (ddd, J = 15.2, 9.4, 4.6 117, 2), 7.19 (1d, J = 8.5, 2.8 Hz, 1H), 259C J 335 5.16 (s, 2H), 3.31 = 3.23 (m, 111), 2.04 (t. J (IM+HI") = 18.9 Hz, 3H), 1.23 (d, J = 6.8 Hz, 6H); ]
I NMR (376 Miz, DMSO-d) & -84.17, -115.86
Synthesis , op ; onl (DMSO-ds) 8 9.57 (s, 1H). 8.33 (s, 1H), 8.24 (d, J =8.5 Hz, 2H), 8.20 - 8.15 (im, 2D, 7.96 (d, J =8.6 Hz, 21D), 7.90 - 7.78 (m, 2H), 7.54 — 7.39 (m, 2D), 7.19 (td, J = 89 3.5.2.8 Iz, IH), 5.16 (s, 211), 3.32 - 3.23 260C J > 5 : =~ - (M+ (m, LID, 1.24 (d, J = 6.8 lz, 61D);
F NMR (376 MHz, DMSO-d) 3 84.02 (1, /=2312),-113.41, -115.87 (DMSO-d) 59.57 (s, 1H), 8.28 (s, LID), 8.23 = 8.15 (m, 410), 8.01 — 7.98 (m, 2H), 7.86 —= 7.78 (mm, 2H), 7.58 (dd, J =8.8, 5.6 Hz, 111), 7.26 (dd, J = 10.4, 3.0 Hz, 1H), 53¢ 7.15 (ddd, J =8.7, 8.0, 3.0 Iz, ILD), 5.10 (s,
AE 539 261C J (IM+H]Y) 2H), 3.28 (1d, J = 6.8, 1.8 Hz, 1H), 1.24 (d. J = 6.8 Hz, 611);
F NMR (376 MHz, DMSO-dq) 3 -60.81, -112.54
NMR spectral data were acquired using a 400 Mllz instrument unless otherwise noted.
Table 4A: Analytical Data for Optically Active Compounds in Table 3
Separation , Chiral | Lend
ID Method MS Purity H NMR (8) (%) (CDCl3) 6 8.58 (s, 1H), 8.31 (s, 1H), 8.23 : 571 (d, J =8.4 Hz, 211), 7.87 — 7.78 (m, 411), 234C A (M+H) 98.73 | 7.41, J=63 Hyg, 3H), 7.37 - 7.31 (m, 1H), 7.28 (d, J = 7.0 Hz, 1H), 4.09 - 3.98 (m, 2H), 2.29 (s, 31) (CDCl3) 88.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J =8.31lz, 21), 7.87 — 7.78 (m, 411), 571 235C A (M+1D) 95.75 | 7.41 (dd, J=7.0,5.6 Hz, 3H), 7.34 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 6.0 Hz, 1H), 4.09 - 3.98 (m, 211), 2.29 (s, 310) 160 1
Separation Chiral $ : yp I 1
ID Method MS I unity HNMR (3) (%) (CDCI,) 8 8.58 (s, LHD, 8.31 (s, LH), 8.23 (d, J=841z 210,781 (dd, J=117,5.1 a 565 A Hz, 41), 7.40 (d, J = 8.4 Hz, 2H). 7.35 (4, 2 a s 236¢ A Tove | 79% 1727.7 10 1D, 7.24 27.08 (am, 200, 4.02 {s,2I1), 2.53 (q, J = 7.5 Hz, 2H), 2.21 (s,
JED. 1.21 (1, J =T7.6 Hz, 3H) (CDCl3) 8 8.58 (s, LIT), 8.31 (s, IT), 8.23 (d.J=84 Hz 2H), 7.81 (dd, J=11.7,5.1
A 565 an | Hz, 4H), 7.40 (d, J =8.3 Hz, 2H), 7.35 “3 2 237C A Men | OF | ads = 10.4, 4.9 117, 110, 7.24 - 7.20 (m, 20), 4.02 (s, 21D), 2.59 = 2.45 (mm, 21D), 2.21 (s, 3H), 1.21 (t, J = 7.6 Hz, 3H) (CDCl3) 3 8.58 (s, 111,829 (d, /=3.9
Liz, 11), 8.23 (d, J = 8.4 Hz. 2H), 7.82 (1, a 579 J =8.8 Hz, 41D), 7.40 (d, J = 8.3 Hz, 3H), 2 / ’ y 238C Many | 2H 731d, 726.9 Hz, 111), 7.19 (dd, J = 76, 5.2 Hz, LH), 4.03 (s, 2H), 2.83 — 2.73 (m1. 1H), 2.21 (s, 3H), 1.25 ~ 1.18 (m, 6H) (CDCl;) 88.58 (s, 1H), 8.30 (s, 1H), 8.22 (t, J =8.7 Hz, 2H), 7.82 (t. / = 8.7 Hz, ; — Q 7 LT; 2 — 239¢ 579 9 63 4H), 7.40 (d. J=82 Hz, 3H), 7.31 (d, J = (M+1D) 8.0 Hz, 1), 7.20 d, J = 7.3 Hz, 111}, 4.03 (s,2H), 2.83 = 2.73 (m, TH), 2.21 (s, 3H), 1.25 — 1.18 (m, 6H)
NMR spectral data were acquired using a 400 MIz instrument unless otherwise noted.
Table 5: Biological Results
Lo % %
Compound Te Ewan Mortality | Mortality
Number ofem? BAW 50 GPA 200
Heem pg/em’ ppm
Number I g/cm? BAW 50 GPA 200
Hg/cm ppm
Cw wa [es
I I A
Ce a ae
Ce a as
Cm a a [e
Number 2 BAW 50 GPA 200 hefem pe/em’ ppm
Cw | a a [eo
EE
Ce |e |e
Tee
Ce [a a o
Number ng/em? BAW 50 GPA 200 pg/em ppm
Cee [wo
Ce [a a [es
Ce | a 63C A A D ic | A A Cp
Ce a a es
Ce [a
} .
Number tg/em’ BAW 50 GPA 200 g/cm ppm
Cw | [a [eo
Cw a
Ce [a ne we eT
Ce a a
Cw ae es
% Mortality | 7 %
Compound CEW 30 Mortality Mortality pg/em ppm
Ce a [a [a
Number 3 BAW 50 GPA 200 ne/em pg/em’ ppm
Cac [a [a
Ce [a a [e
Ce a a
Number ngfem’ BAW 50 GPA 200 pg/em ppm we a [a a]
Ce [a a [es ; ; we a a |e]
Number | 0% BAWS0 | GPA 200 pg/cm ppm re a TT ae
Number 5 BAW 50 GPA 200 hefem pe/em’ ppm
Cw [a a [a we | oa | oa |e] we | oa oa |p owe | oa | oa |p
Coc [a [a [es
Number 2 BAW 50 GPA 200 hgfem ug/em’ ppm
Co a | a [a ;
.
J
Number 3 BAW 50 GPA 200
Hg/em g/cm” ppm
Co
. % %
Compound 7 Moria Mortality | Mortality
Number 2 BAW S50 | GPA 200
Hg/em ug/em’ ppm

Claims (7)

CLAIM < oo
1. A molecule according to Formula Two Si . PN ar Het ~ .N2__S “4 Aff Arr ONT ST F N3-RS R4 Formula 2 wherein: (a) Ari is substituted phenyl having one or more substituents independently selected from C,-C¢ haloalkyl and C;-C¢ haloalkoxy; (b) Het is 1,2,4-triazolyl N £ = ——Ar=, ~~ MN / Ary N . ’ : (c) Ar; is phenyl; (d) RlisH or Ci-Cs alkyl, (2) R4 is phenyl substituted with one or more substituents independently selected from F, Cl, Br, I, and C1-Cs alkyl; (h) RS is a 1 membered saturated hydrocarbyl linkage.
2 A molecule according to claim 1 wherein said molecule is selected from /~N \ = : 240C | £70 Nay? : ~N F Lr N ~ i
/~N
NA. STOLL 242 | F70 ~ es! 7 \ O0— NN zz « F | N >) 243C 5 IT OL F = z NE F CY N S— we pe 0 Ct NN LCL 245C Fo A _N-NZ TN F bg CN 2 NCL 246C 5-0 _N-NZ~N Cl ; i F NTN S : FL Lr Tx Ay 247C Fsto ANN F /\ ~N wal Rl 5 248C E30 So Noy? : 175 4 i /=N S No Cron 249C | © ZNT TN FO =
F . Ne /~N AL =~ 250C ~ NA E +O aN ==\, NN oA J NL S— 251C NAY Orr FF F—=( a 252C Soe N A FF Ho 253C UN Ah ¥ "J — F “NN oJ) NTNF S 254C “ Lon LY :
FF ~~ ./~N . . N. ~ ir NZ NF S— He FL /~<N \, F = — TOA S— 256C J “And Oy — F hs CO Na - f ML > 257C “e “ NA] F 5 o F /~<N +5 _ 258C c A yr /~N yr OL N S F ~ 259C NA pF THO PY Cl > 260C | on U3 Or NL J : F \ J N Cl s— : 261C soe N An : F
3. A composition comprising a molecule according to claims 1 or 2 and a carrier.
4. A composition according to claim 3 further comprising at least one other compound : : selected from the Insecticide Group, Acaricide Group, Nematicide Group, Fungicide Group, Herbicide Group, AI Group, or Synergist Group.
5. A composition according to claim 3 further comprising a seed.
6. A composition according to claim 3 and at least one compound that has a mode of action selected from acetylcholinesterase inhibitor, sodium channel modulator, chitin biosynthesis inhibitor, GABA-gated chloride channel antagonist, GABA and glutamate-gated chloride channel agonist, acetylcholine receptor agonist, MET I inhibitor, Mg-stimulated ATPase inhibitor, nicotinic acetylcholine receptor, Midgut membrane disrupter, oxidative phosphorylation disrupter, and ryanodine receptor (RyRs).
:
7. A process comprising applying a composition according to claim 3 to an area to control a pest, in an amount sufficient to control such pest. : 178 : P
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